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  • 1980-1984  (788)
  • 1980  (788)
  • Chemical Engineering  (478)
  • Biochemistry and Biotechnology  (252)
  • pharmacokinetics
  • Nuclear reactions
Source
Material
Years
  • 1980-1984  (788)
Year
Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Melatonin administration to dogs (1980)
    Springer
    Journal of neural transmission 49 (1980), S. 281-285 
    Details
    ISSN: 1435-1463
    Keywords: Melatonin administration ; diurnal rhythm ; dog ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Melatonin concentrations in serum and urine were examined following oral administration of melatonin to dogs. Four different doses of melatonin ranging from 10 to 80 mg per kg of body weight were given. Melatonin was rapidly absorbed and reached a maximum serum level after 20–30 min, with a distribution phase of 3.5 hours and elimination half life (t1/2) of 5 hours. The fraction excreted in the urine was 0.25% of the administrated dose during the first 5 hours. These results as well as the diurnal rhythm of serum melatonin in the dog are similar to corresponding data reported in the human.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01252131
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  • 2
    Electronic Resource
    Electronic Resource
    Metabolic effects and pharmacokinetics of intravenously administered dichloroacetate in humans (1980)
    Springer
    Diabetologia 19 (1980), S. 109-113 
    Details
    ISSN: 1432-0428
    Keywords: Dichloroacetate ; pharmacokinetics ; lactate ; lactic acidosis ; alanine ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dichloroacetate decreases plasma glucose, lactate, and alanine concentrations in normal and diabetic subjects, and lowers lactate concentrations and increases survival in animals with experimentally induced lactic acidosis. The relationship between these effects and plasma dichloroacetate concentrations have not been previously studied in man. Dichloroacetate (1–50 mg/kg) was infused over 30 min to 16 healthy subjects and plasma drug concentrations were followed by gas chromatography over the next 8 h. Peak plasma concentrations were linearly related to the dose (r = 0.98, p〈0.001) up to 30 mg/kg, above which 4 of 7 subjects had disproportionately high plasma drug concentrations. Nonlinear disposition was also indicated by the convex decreasing plasma elimination curves; levels declining less rapidly initially than later. At plasma concentrations below 10 μg/ml, elimination was monoexponential with a half-life of 32±11 min (mean±SD). Plasma drug clearance also decreased with doses greater than 20 mg/kg. Within 2 h of administration of the maximally effective dichloroacetate dose of 35 mg/kg, plasma lactate concentrations fell 75% below baseline and alanine fell 50% below baseline, while blood glucose was unaffected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00421855
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sodium valproate in epileptic patients: Prediction of maintenance dosage by single-dose study (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 71-77 
    Details
    ISSN: 1432-1041
    Keywords: sodium valproate ; epileptic patients ; pharmacokinetics ; plasma concentration ; prediction ; maintenance dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic analysis of the plasma valproic acid concentration-time course, following a single oral dose (600 mg) of sodium valproate, was performed in 20 epileptic patients as an aid to the prediction of a proper chronic dosage regimen. A simple one-compartment model was found inadequate to describe the drug concentration-time course in 15 of the 20 patients studied. The average elimination (β phase) half-life of 9 h was shorter than that previously reported in healthy subjects. The latter observation and the wide variation in plasma valproic acid clearance observed between patients (0.09–0.53 ml/kg/min) may have been related to its altered disposition by concomitant anticonvulsant therapy. Sodium valproate maintenance therapy, determined by single-dose pharmacokinetic prediction of steady-state plasma valproic acid levels, did not require dosage adjustment because of unwanted effects. However, the occurrence of drug-related adverse events led to dosage reduction in 4 of 9 patients whose chronic therapy was not pharmacokinetically predicted. Moreover, the pharmacokinetic variability demonstrated for sodium valproate by patients on multiple therapy, whose chronic sodium valproate therapy was pharmacokinetically predicted, indicates the value of monitoring plasma valproic acid levels for the regulation of anticonvulsant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561679
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  • 4
    Electronic Resource
    Electronic Resource
    Metabolic and haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, in man (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 81-86 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; beta1-adrenoceptor agonist ; metabolic effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic and haemodynamic effects of three intravenous doses (0.5, 1.0 and 4.0 mg) of prenalterol, a selective β1-adrenoceptor agonist, were studied in 10 healthy male subjects. Plasma levels of prenalterol during the experiments were related to the haemodynamic effects. Prenalterol induced a dose-dependent increase in systolic blood pressure and heart rate. The maximal effects amounted to about 30 mm Hg and 15 beats/min, respectively, after the highest dose (4.0 mg). The diastolic blood pressure fell by a maximum of about 15 mm Hg. The effect of prenalterol on systolic blood pressure and heart rate persisted for about 3 h after the end of the last infusion, whereas that on diastolic blood pressure only lasted for 60 min. Compared with placebo, there was a moderate increase in plasma FFA and glycerol. A small rise in insulin level was also recorded, but no significant change was seen in other metabolic variables — triglycerides, glucose, lactate, pyruvate. Serum potassium tended to decrease and serum sodium was unchanged. The initial distribution of prenalterol was rapid (half-life 7 min) and the overall elimination rate corresponded to a plasma half-life of 2 h. A linear relationship was found between the plasma level of prenalterol and its effects on systolic blood pressure and heart rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562614
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of zimelidine (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    Details
    ISSN: 1432-1041
    Keywords: zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562618
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  • 6
    Electronic Resource
    Electronic Resource
    Plasma and salivary pharmacokinetics of dapsone estimated by a thin layer chromatographic method (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 129-133 
    Details
    ISSN: 1432-1041
    Keywords: dapsone ; salivary drug elimination ; pharmacokinetics ; acetylator phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A high performance thin layer chromatographic assay for dapsone is described with a minimum level of detection of 20 ng ml−1 which is suitable for the study of dapsone pharmacokinetics in plasma and saliva. 100 mg dapsone was administered orally to seven normal adult volunteers, the mean plasma pharmacokinetic parameters were: α=0.23 h−1; β=0.0236 h−1, and t1/2β=30.2 h. Dapsone is also eliminated into the saliva and the t1/2 may be determined via its estimation in saliva. It is 73% bound to plasma protein and the saliva/plasma concentration ratio was found to be 27%. In two subjects the free plasma dapsone concentration was identical to the simultaneous salivary dapsone concentration. Therefore the salivary dapsone concentration is a measure of the free plasma fraction of dapsone. Saliva/plasma dapsone concentration ratios show no time or concentration dependence and little inter-individual variation but are unsuitable for acetylator phenotype determination because monoacetyldapsone is not eliminated in the saliva.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562621
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sotalol after chronic administration to patients with renal insufficiency (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 321-326 
    Details
    ISSN: 1432-1041
    Keywords: sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten hypertensive patients with moderate to severe impairment of renal function were treated with sotalol for 5 to 10 weeks (average 6.4 weeks). Dosage was individually titrated (range 80 to 480 mg daily). The drug was given once daily in the morning. In eight patients blood pressure was satisfactorily controlled. Higher steady-state levels were observed than have been reported after similar doses in patients with normal renal function. The apparent first-order elimination rate constant and plasma clearance were significantly correlated with glomerular filtration rate. For an anuric patient, serum half-life was calculated to be 69 h. In relation to the raised plasma levels, side effects were uncommon. Since sotalol is excreted predominantly via the kidney, therapy in patients with impaired renal function should start with a low dose and any increase in dosage should be made carefully. As the anti-hypertensive effect does not appear to be correlated with the plasma level or with tolerance, adjustment of dose should be based on clinical response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561389
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  • 8
    Electronic Resource
    Electronic Resource
    Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 517-520 
    Details
    ISSN: 1432-1041
    Keywords: desmethyldiazepam ; oxazepam ; cimetidine ; hepatic elimination ; pharmacokinetics ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of single oral doses of desmethyldiazepam 20 mg or oxazepam 50 mg were studied in 5 healthy volunteers under controlled conditions, before and following a 24 h pretreatment with cimetidine 200 mg×5. Cimetidine significantly impaired (p=0.03) the elimination of desmethyldiazepam, as shown prolongation of its elimination half-life from 51.7±21.9 h to 72.6±39.4 h (mean ± SD), and a decrease in total plasma clearance from 12.0±2.7 ml/min to 8.6±3.3 ml/min. The disposition of oxazepam was not affected. From these results, and recently published data on diazepam and chlordiazepoxide, it is concluded that cimetidine impairs the hepatic elimination of those benzodiazepines which are metabolized by phase I reactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874666
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  • 9
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics of alcuronium chloride in man (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 449-457 
    Details
    ISSN: 1432-1041
    Keywords: alcuronium ; single dose ; multiple dose ; plasma levels ; neuromuscular response ; pharmacokinetics ; anaesthesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic behaviour of alcuronium is described for nineteen patients undergoing anaesthesia for elective surgery. Eleven patients received a single bolus intravenous dose of 0.25 mg/kg, while 8 patients required additional doses of 0.125 mg/kg. A two-compartment open model was found to describe adequately both the single dose and multiple dose data for the majority of patients. No significant differences were found in the model-independent pharmacokinetic parameters between the single and multiple dose studies. Mean values for the pooled data for the half-life (t1/2β), apparent volume of distribution (Vdβ), volume of distribution at steady-state (Vdss), volume of the central compartment (Vc) and plasma clearance (Clp) were 198.75 min, 24.261, 20.891, 8.181 and 90.22 ml/min respectively. Evoked muscle twitch response was monitored in 17 of the patients to assess the degree of relaxant blockade. The bolus dose of alcuronium produced complete block in 9 patients and between 95 and 99% block in the remainder. The time of onset to maximum block ranged from 3 to 30 min with the concurrently measured plasma levels of alcuronium being 0.79 to 2.25 µg/ml. The time taken following bolus administration to 5% recovery (95% paralysis) was a mean of 42 min and the corresponding mean alcuronium plasma concentration was 0.78 µg/ml.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570163
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  • 10
    Electronic Resource
    Electronic Resource
    Paracetamol pharmacokinetics in thyroid disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 269-273 
    Details
    ISSN: 1432-1041
    Keywords: paracetamol ; thyrotoxicosis ; hypothyroidism ; drug disposition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, distribution and elimination of oral paracetamol have been studied in patients before and after treatment of thyrotoxicosis (n=7) and hypothyroidism (n=4). Absorption was faster in patients with untreated thyrotoxicosis than when subsequently euthyroid. The peak paracetamol concentration, however, was lower in thyrotoxic patients due to an apparent increase in the total body clearance and a shorter plasma half-life. Both absorption and elimination rates were reduced in hypothyroid patients, but were not significantly different from the euthyroid results. When estimated using a two compartment model the total volume of distribution and the hybrid distribution rate constants were unrelated to thyroid status, but the apparent volume of the central compartment was significantly greater in the thyrotoxic group. These changes in drug disposition may contribute to differences in drug response seen in thyroid disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563010
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  • 11
    Electronic Resource
    Electronic Resource
    Pharmacokinetic of 2-(p-methylallylaminophenyl) propionic acid, alminoprofene, in man after single and multiple oral doses (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 419-422 
    Details
    ISSN: 1432-1041
    Keywords: alminoprofene ; antalgic ; pharmacokinetics ; single dose ; multiple doses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 2-(p-methylallylaminophenyl) propionic acid, alminoprofene (INN), a new antalgic drug, was administered orally to men as a single (300 mg) and multiple doses (300 mg three times daily). Plasma and urine concentrations of alminoprofene were determined by gas-liquid chromatography. After the single oral dose, the peak plasma level (36.2 to 41.5 mg/l) was reached within 0.5–1.5 h. The biological half-life ranged from 2.5 to 3.2 h. During chronic administration of alminoprofene, steady-state equilibrium quilibrium was etablished within 24 h. The urinary excretion of alminoprofene as unchanged product and as glucuronide was very important.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636796
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  • 12
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and oral bioavailability of pyridostigmine in man (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 423-428 
    Details
    ISSN: 1432-1041
    Keywords: pyridostigmine ; myasthenia gravis ; pharmacokinetics ; bioavailability ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of pyridostigmine was evaluated after intravenous injection in two healthy male volunteers and after oral administration to five subjects. Plasma concentrations of pyridostigmine were determined after ion pair extraction from plasma and analysis by gas chromatography — mass spectrometry with chemical ionization, using d6-pyridostigmine as internal standard. Degradation of pyridostigmine in vitro was compensated for by use of the deuterated internal standard and by rapid cooling and separation of plasma after blood sampling. After intravenous administration of pyridostigmine 2.5 mg the plasma elimination half-life was 1.52 h, the volume of distribution was 1.43 l/kg and the plasma clearance 0.65 l/kg × h. The pharmacokinetic constants were very similar after oral administration of pyridostigmine 120 mg; the elimination half-life was 1.78±0.24 h, the volume of distribution 1.64±0.29 l/kg and the plasma clearance was 0.66±0.22 l/kg × h. The bioavailability was calculated to be 7.6±2.4%. When pyridostigmine was taken together with food, the time to reach the peak plasma concentration was prolonged from 1.7 to 3.2 h. Bioavailability, however, was not influenced by concomitant food intake. “Steady-state” plasma concentrations of pyridostigmine were measured in myasthenic patients on their ordinary dose schedule of cholinesterase inhibitor drugs. More than a seven-fold difference in steady-state plasma concentration was found between patients taking approximately the same daily dose of pyridostigmine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636797
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  • 13
    Electronic Resource
    Electronic Resource
    Rapid prediction of steady-state serum theophylline concentration in patients treated with intravenous aminophylline (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 473-477 
    Details
    ISSN: 1432-1041
    Keywords: aminophylline ; asthma ; serum theophylline ; pharmacokinetics ; prediction of serum level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 15 acutely ill asthmatics the steady-state serum theophylline concentration was predicted by the method of Chiou et al. using two serum concentration measurements obtained 1 and 5h after starting a continuous infusion of aminophylline. Two theophylline assays with different precision characteristics were compared. With a precise HPLC-assay the prediction was excellent: prediction error (predicted minus measured concentration)=−0.22±1.97 mg/l (mean ± SD); r=0.922. When the theophylline concentration was determined by a rapid enzyme immunoassay of lower precision, but convenient for clinical use, the prediction was less accurate (prediction error=0.58±3.88, r=0.852). However, it was still clearly superior to dosing recommendations based on the population average of theophylline clearance, even after taking into consideration the effect of smoking, congestive heart failure and cirrhosis (prediction error=3.62±13.36, r=0.560). As employed in this study, the method may be useful in helping the physician to choose the optimal dose in severely ill asthmatics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874658
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  • 14
    Electronic Resource
    Electronic Resource
    Lack of pharmacokinetic interaction of colestipol and fenofibrate in volunteers (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 459-463 
    Details
    ISSN: 1432-1041
    Keywords: colestipol ; fenofibrate ; fenofibric acid ; pharmacokinetics ; interaction ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possibility of a pharmacokinetic interaction between two hypolipidemic drugs, colestipol, an ion exchange resin, and fenofibrate, a phenoxyacid derivative, was studied in 6 male volunteers. The investigation followed a four-step protocol during 18 days, and relied on determination of plasma and urinary levels of fenofibric acid, the active metabolite of fenofibrate. The kinetics of a single dose of fenofibrate 300 mg was established over 3 days. Thereafter, from Days 4 to 9 fenofibrate was given daily as 200 mg in the morning and 100 mg in the evening; the plasma fenofibric acid level reached about 10 µg/ml. From Days 9 to 15 the same dose of fenofibrate was administered together with colestipol 10 g in the morning and 5 g in the evening. Plasma fenofibric acid concentrations remained unchanged and the 24 h urinary excretion of fenofibric acid did not fall. On Day 15, a last single dose of fenofibrate 300 mg was given with colestipol 15 g. The pharmacokinetic pattern of fenofibric acid on Days 15 to 18 did not differ significantly from that found previously (Days 1 to 3). From these results, it is likely that there is no pharmacokinetic interaction between the two hypolipidemic drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570164
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  • 15
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and clinical response (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 51-53 
    Details
    ISSN: 1432-1041
    Keywords: pethidine ; phenobarbital ; aminoglycoside antibiotics ; pharmacokinetics ; clinical response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561478
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  • 16
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of diuretics and methylxanthines in the neonate (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 55-63 
    Details
    ISSN: 1432-1041
    Keywords: diuretics ; furosemide ; caffeine ; theophylline ; neonate ; pharmacokinetics ; disposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination of diuretics and methylxanthines is considerably slower in the neonate than in the adult. Dose guidelines, especially during long term maintenance, must be adjusted to account for this slower drug elimination. Pharmacokinetic studies and the requisite pharmacologic evaluation on diuretics such as hydrochlorothiazide, spironolactone, ethacrynic acid and others should be done. Furosemide undergoes biotransformation in the newborn producing an acid metabolite and a glucuronide conjugate. Methylxanthines are effective in the treatment of neonatal apnea. Plasma elimination of theophylline is exceedingly slow, more so with caffeine. Decreased elimination is partly explained by decreased oxidative biotransformation. Caffeine is excreted in the urine of the newborn mainly unchanged (85%) in contrast to the adult where caffeine is a minor portion of urinary excretion (2%). Theophylline is methylated to caffeine and may possibly exert additive pharmacologic effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561479
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  • 17
    Electronic Resource
    Electronic Resource
    Absorption and disposition of ampicillin in the elderly (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 195-198 
    Details
    ISSN: 1432-1041
    Keywords: ampicillin ; age ; oral dose ; i. v. dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ampicillin (500 mg) was administered intravenously (i. v.) and orally to a small panel of young and elderly subjects in a cross-over fashion. Plasma concentrations of ampicillin were measured by a fluorimetric technique for 8 h following dosage. A two compartment-open model was used to characterise the plasma concentration-time data for the intravenous study, and a one compartment-open model incorporating an absorption lag time and a first-order absorption rate constant for the oral data. Plasma clearance after i. v. ampicillin was found to be significantly decreased in the elderly (P〈0.05, 0.08 1 h−1kg−1 versus 0.18 1 h−1kg−1), and half life and area under the plasma level-time curve were significantly increased (P〈0.05, 6.70 h versus 1.68 h, t1/2β; p〈0.01, 176.51 µg·h ml−1 versus 37.88 µg·h ml−1, AUC o ∞ ) as compared to the young. No sigificant differences were observed between the age groups for the volume of distribution terms and the changes in drug handling noted in the elderly were attributed to a decrease in the renal elimination of ampicillin. Following oral administration a significant increase in t1/2β, AUC o ∞ and the maximum plasma concentration (Cpmax P〈0.01, 6.59 µg ml−1 versus 3.42 µg ml−1) of ampicillin was found in the elderly subjects. These findings were similarly attributed to a decrease in drug elimination in the aged, since no apparent age differences were noted in the pharmacokinetic parameters governing both rate and extent of ampicillin absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561590
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  • 18
    Electronic Resource
    Electronic Resource
    Effects and pharmacokinetics of isosorbide dinitrate in normal man (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 237-244 
    Details
    ISSN: 1432-1041
    Keywords: isosorbide dinitrate ; 2-isosorbide mononitrate ; 5-isosorbide mononitrate ; digital plethysmography ; hypotension ; bradycardia ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 18 subjects were given isosorbide dinitrate (ISDN) 5 mg sublingually and serum concentrations of ISDN, 2-isosorbide mononitrate (2-ISMN) and 5-isosorbide mononitrate (5-ISMN) were measured, as well as changes in digital plethysmographic amplitude, heart rate, ECG, blood pressure and Schellong's test. ISDN was rapidly absorbed and metabolized, having an elimination half-life of 29 min. Its metabolites 2-ISMN and 5-ISMN had longer half-lives of 1.75 and 7.6 h respectively. The amplitude of the α-wave of the digital plethysmograph did not change significantly either in the predrug period or after placebo administration. It increased within 4 min of administration of ISDN, and reached a maximum after 14 min; the effect lasted for about 2 h. ISDN lowers blood pressure and increases heart rate in most volunteers, but in 3 of the 18 subjects severe hypotension occurred, accompanied by severe, reversible bradycardia, which was probably due to vagal reflexes initiated by the markedly diminished ventricular enddiastolic volume (LVEDV) and pressure (LVEDP). No correlation could be demonstrated between the serum concentration of ISDN and/or its vasoactive metabolites and changes in plethysmographic amplitude.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563005
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  • 19
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics and oral bioavailability of ketobemidone (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 45-50 
    Details
    ISSN: 1432-1041
    Keywords: ketobemidone ; narcotic analgesic ; N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The basic pharmacokinetics and oral bioavailability of ketobemidone have been studied in 6 patients after surgery. Plasma concentrations were first determined following intravenous administration of Ketogin® 2 ml, containing ketobemidone chloride 10 mg and the spasmolytic N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride 50 mg, and then, on the second postoperative day, following oral administration of 2 tablets of Ketogin®, each containing ketobemidone chloride 5 mg and the spasmolytic agent 25 mg. The average oral bioavailability of ketobemidone was 34%±16% (SD, n=6). The mean plasma half-life of elimination (t1/2β) was about the same following oral (2.45±0.73 h; SD, n=5) as after intravenous administration (2.25±0.35 h; SD, n=6). The low oral bioavailability and rapid elimination of ketobemidone demonstrated in this study suggest that the usual dosage recommendation for oral Ketogin® (ketobemidone 5–10 mg every 6–7 h) in patients with severe pain is too low.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561676
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  • 20
    Electronic Resource
    Electronic Resource
    A single and multiple dose pharmacokinetic and pharmacodynamic comparison of conventional and slow-release metoprolol (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 87-92 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocker ; metoprolol ; slow-release formulation ; multiple dosing ; blood pressure ; heart rate ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and pharmacodynamic profiles for metoprolol have been measured in six healthy volunteers after single and multiple dosing with 100 mg conventional formulation twice daily and 200 mg slow-release formulation once daily. Both multidose regimes produced measurable predosing plasma concentrations of metoprolol. The plasma concentrations on the eighth day were greater than predicted by the single-dose data as indicated by the comparison of the total areas under the curve for the single dose and the dosage interval areas during multiple dosing. This increase may be associated with a change in the bioavailability and/or clearance of the drug and is currently being investigated. The peak concentrations for the two regimens were comparable but the times to peak with the slow-release regimen were significantly delayed. Both regimes produced significant beta-blocking effects over 24 h during multiple dosing, the reductions in exercise heart rate at 0 and 24 h on the eighth day corresponding to more than 20% of the maximum effect. Resting pulse rates and blood pressures were affected to a similar extent by the two regimens but neither significantly altered respiratory peak flow rates. The effects during multiple dosing were generally greater than those after a single dose and appeared to follow a more consistent trend. This observation, together with those for the plasma level data on the eighth day, illustrate the importance of performing multiple-dose studies in assessing beta-blocking drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562615
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  • 21
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and clinical observations on prolonged administration of flunitrazepam (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 189-196 
    Details
    ISSN: 1432-1041
    Keywords: flunitrazepam ; prolonged administration ; pharmacokinetics ; clinical observations ; sleep parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight patients were given flunitrazepam 2 mg orally, once daily for 28 consecutive days. The time-course of the plasma concentration of unchanged flunitrazepam and its principal metabolites were studied in detail after the first and last doses. Additional blood samples were collected immediately before administration of the tablet on days 4, 7, 11, 14, 18, 21 and 25. Clinically there were no changes during the trial period in the onset of sleep, duration of sleep, depth of sleep measured as number of spontaneous awakenings, or in the patients' condition on awakening. The time-course of the plasma concentration of flunitrazepam could be described by a three-compartment model, assuming that the rate constants remained unchanged during treatment. Maximal plasma concentrations of unchanged flunitrazepam, found two hours after intake, reached 10–15 ng/ml after the first and 15–20 ng/ml after the last dose. The β-half-life was found to be between 20 and 36 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561899
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  • 22
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of chlormethiazole in healthy volunteers and patients with cirrhosis of the liver (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 275-284 
    Details
    ISSN: 1432-1041
    Keywords: chlormethiazole ; cirrhosis of the liver ; antipyrine ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole after oral and intravenous administration was studied in six healthy volunteers and eight patients with alcoholic cirrhosis of the liver. Plasma concentration-time curve after the intravenous infusion could adequately be described by two- or three-compartment open models both in healthy volunteers and in the patients. Based on the areas under the plasma concentration-time curves, the systemic bioavailability of oral chlormethiazole was about ten times greater in the patients than in healthy controls. The elimination of chlormethiazole was relatively less retarded in the patients, as indicated by a decrease of about 30% in its plasma clearance. In the patients the plasma protein binding of chlormethiazole was decreased, but the volume of distribution and half-life of elimination were unchanged. The increase in bioavailability of chlormethiazole was associated with significant alteration in the serum levels of bilirubin, albumin, alkaline phosphatase, prothrombin-proconvertin activity (P + P) and elimination rate of antipyrine or14C-aminopyrine. The increased bioavailability of oral chlormethiazole was due to impaired first-pass metabolism in the cirrhotic liver. A considerable reduction in dose seems to be indicated if oral chlormethiazole is used in patients with advanced cirrhosis of the liver. A substantial fraction of dose, averaging 15%, was lost during the intravenous infusion, presumably due to adsorption to the infusion tubing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00625801
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  • 23
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of naproxen in subjects with normal and impaired renal function (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 263-268 
    Details
    ISSN: 1432-1041
    Keywords: naproxen ; renal insufficiency ; metabolism ; protein binding ; single dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of naproxen after a single oral dose of 250 mg has been studied in 8 subjects with normal renal function and 16 patients with varying degrees of chronic renal insufficiency. Unchanged naproxen and its main unconjugated metabolite, 6-0-desmethylnaproxen, were determined fluorometrically in serum. In healthy subjects the elimination half-life of naproxen was 17.7± 3.0 h (mean±SD) and it was not significantly prolonged in patients with renal failure (18.1±5.3) h. No accumulation of naproxen in serum occurred in uraemic patients. On the contrary, serum drug levels were slightly but significantly lower in patients with severe renal failure. The total body clearance and apparent volume of distribution of naproxen were significantly increased in this group of patients. Decreased binding of naproxen to serum proteins was observed in patients with renal failure. The apparent half-life of desmethylnaproxen was of the same order of magnitude as that of naproxen (18.6± 4.4 h), and was also independent of renal function. A good correlation was found between the area under the curve (AUC), the peak concentration of the metabolite and the serum creatinine concentration. These observations suggest increased metabolism and an increased apparent volume of distribution of naproxen in severe renal failure, probably caused by decreased serum protein binding of the drug. However, it is proposed that in naproxen therapy no adjustment of the dosage regimen is necessary in patients with impaired renal function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563009
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  • 24
    Electronic Resource
    Electronic Resource
    Pharmacokinetic studies in volunteers of intravenous and oral cis (Z)-flupentixol and intramuscular cis (Z)-flupentixol decanoate in viscoleo® (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 355-360 
    Details
    ISSN: 1432-1041
    Keywords: cis (Z)-flupentixol ; cis (Z)-flupentixol decanoate ; serum concentration ; biological half-life ; pharmacokinetics ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum concentrations of cis (Z)-flupentixol have been estimated in three male human volunteers who received cis (Z)-flupentixol by intravenous infusion, flupentixol (cis (Z)/trans (E) mixture, 1:1) orally as single and repeated doses, and i. m. cis (Z)-flupentixol decanoate in Viscoleo®. The intravenous data show that cis (Z)-flupentixol followed a multicompartment model, but it was not possible to fit the data to a two or three compartment model. The concentration curves after oral administration indicated relatively slow absorption with a peak concentration at 3–6 h, except for one case with peak at 1 h. The variation in the dosage interval after one daily oral administration was relatively limited (1.7–3.0 times), which indicates that 24 h is a reasonable dosage interval. Biological half-lives were estimated in different ways and showed some intra-individual variation; the half-life was of medium length (19–39 h). The serum concentrations after intramuscular injection of cis (Z)-flupentixol decanoate clearly demonstrated a depot effect, with a maximal concentration at 3–5 days after injection. The descending part of the serum curves allowed an approximate estimation of half-life of 3–8 days. This was not the elimination half-life, but in all probability the half-life of release of drug from the oil depot which was the rate-limiting step. From the areas under the serum concentration curves the fraction of orally administered cis (Z)-flupentixol available to the organism was calculated to be 55% (range 48–60%). The loss of drug might have been due to imcomplete absorption, but it is more likely that cis (Z)-flupentixol underwent first-pass metabolism in the gut wall and the liver. As the tablets contained about 50% cis (Z)-flupentixol, while the depot preparation contained 74% cis (Z)-flupentixol, the pharmacokinetically equivalent doses are: 10 mg tablet daily corresponds to 25 mg depot weekly. Calculation of systemic clearance gave values of 0.44–0.49 l/min, and an apparent volume of distribution was 12.5–17.2 l/kg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561395
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  • 25
    Electronic Resource
    Electronic Resource
    Time-course of the anti-hypertensive action of atenolol: Comparison of response to first dose and to maintained oral administration (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 365-374 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636787
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  • 26
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of acebutolol in patients with all grades of renal failure (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 339-348 
    Details
    ISSN: 1432-1041
    Keywords: acebutolol ; renal failure ; dialysis ; pharmacokinetics ; N-acetylmetabolite
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of acebutolol was studied in 10 healthy subjects with normal renal function (RN), in 13 patients with various degrees of renal failure (RI) and in 8 patients undergoing repeated haemodialysis (RD). A highly specific method was used to measure acebutolol (A) and N-acetylmetabolite (NAM). In RN the decrease in plasma levels was biexponential with an apparent plasma half lives in the slow phase of A: 8.8±2.3 h and NAM: 11.4±2.2 h. The percentage of the dose excreted unchanged was 13.9% and as NAM 25.8%. Renal clearances were A: 167±20 ml/min and NAM: 150±18 ml/min. The apparent plasma half life of acebutolol does not change according to the degree of renal insufficiency (RI: 7.0±2.7 h, RD: 7.5±2.7 h), while that of NAM is increased (RI: 21.5±10.1 h, RD: 32.3±16.8 h). There is a linear relationship between the apparent elimination rate constant of NAM and creatinine clearance (r=0.832,p〈0.001). In RI 21.7% of the dose is excreted in urine (A 5.0%, NAM 16.7%). When renal function is impaired, the renal clearance of A and NAM decrease in parallel with the creatinine clearance (A: r=0.874,p〈0.001; NAM: r=0.954,p〈0.001). During dialysis the plasma half life fell (A=3.4±0.9 h, NAM=7.4±2.6 h). The dialytic clearance was A: 42.6±12.7 ml/min and NAM: 40.4±16.3 ml/min, for a blood flow of 238±35 ml/min through a dialyser with a cuprophane membrane (Ultraflo II Travenol). Acebutolol is taken up by erythrocytes (λbc=0.50±0.04). The results suggest that the dosage of acebutolol should be adjusted according to the degree of renal insufficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558446
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  • 27
    Electronic Resource
    Electronic Resource
    Disposition and clinical pharmacokinetics of microcrystalline theophylline (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 379-384 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558452
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  • 28
    Electronic Resource
    Electronic Resource
    Relationship of propranolol pharmacokinetics to antihypertensive effect and beta-adrenergic blockade in the treatment of hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 391-394 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636790
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  • 29
    Electronic Resource
    Electronic Resource
    Influence of food intake on the absorption and effect of glipizide in diabetics and in healthy subjects (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 279-283 
    Details
    ISSN: 1432-1041
    Keywords: glipizide ; diabetes ; food intake ; blood glucose ; blood insulin ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of a standardized breakfast on the single dose (5 mg) kinetics and effects of glipizide was examined in 9 healthy volunteers and in 14 diabetics not previously exposed to a sulfonylurea. In the volunteers, glipizide caused an increase in plasma insulin and a reduction in blood glucose both during continued fasting and when the drug was taken with the breakfast. Food intake did not influence the peak concentration, the elimination half-life or the bioavailability of the drug. However, food intake significantly delayed the absorption of glipizide by about 0.5 h. In the patients, glipizide produced a significant increase in plasma insulin and a significant diminution of the rise in blood glucose in response to the meal. Starting at breakfast and for 45 min thereafter serum glipizide concentrations were significantly higher when the drug was taken 0.5 h before the meal, than when ingested concurrently with it. With the former treatment, the increase in plasma insulin occurred earlier and the blood glucose reduction was pronouncedly greater than with the latter treatment. As the absorption of glipizide may be delayed by concurrent breakfast, this may help to explain, why the administration of glipizide 0.5 h before breakfast led to a more appropriate relation between the serum concentration of the drug and the metabolic impact of the meal, thereby promoting more appropriate insulin release and better glucose disposition than after concurrent intake of the drug and breakfast.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563012
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  • 30
    Electronic Resource
    Electronic Resource
    Disposition of dibekacin in patients undergoing haemodialysis (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 347-350 
    Details
    ISSN: 1432-1041
    Keywords: dibekacin ; renal failure ; dialysis ; pharmacokinetics ; microbiological assay ; dosage regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Dibekacin were studied in 10 patients with terminal renal impairment (creatinine clearance 〈5 ml/min) undergoing haemodialysis sessions lasting 4 h. The dialyzers were either the Gambro Lundia Major 13.5 or the Ultra Flo II 1.4., and the patients were divided into two groups according to the dialyzer used. Blood flow varied between 250 and 280 ml/min and dialyzate flow between 450 and 600 ml/min. All patients received a single i. v. dose of Dibekacin 1.5 mg/kg at the beginning of the dialysis session. The concentration of the antibiotic at the input and the output of the dialyzer were determined microbiologically by a plate diffusion method usingB. subtilis as the test organism. The intravenously administered antibiotic followed an open two-compartment kinetic model. The type of dialyzer used did not influence the dialysis of Dibekacin. Haemodialysis significantly increased the elimination rate of the antibiotic with respect to the interdialysis periods. The plasma half-life in the slow disposition phase fell from 30 h in the interdialysis period to 4.0 h during dialysis sessions. From the calculated pharmacokinetic parameters, a dosage regimen for this kind of patient is proposed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561393
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  • 31
    Electronic Resource
    Electronic Resource
    Haemodynamic effects, plasma concentrations and tolerance of orally administered prenalterol in man (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 383-390 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; oxprenolol ; haemodynamics ; pharmacokinetics ; inotropic effects ; side effects ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prenalterol was studied in six healthy volunteers given single oral doses of 2.5, 5 and 10 mg and placebo. It displayed a distinct positive inotropic action, manifested as a dose-related reduction of 16.5–27.2 msec in the pre-ejection period (PEPc; systolic time-intervals), and an increase of 4.2–5.9 Ω/sec2 in the Heather index (impedance cardiography). There was also a dose-related increase of 17.6–34.0 mmHg in systolic blood pressure, whereas diastolic pressure showed a slight, transient decrease, not related to the dose given. Heart rate rose by 5–12 beats/min. Stroke volume, as determined by impedance cardiography, increased by 24.2–28.5 ml at all three dose-levels. The effects of the drug developed rapidly, reaching their maximum within 30–60 min and lasting for about 4 h. The time-course of the effects corresponded to the plasma concentrations of the drug. The increases in systolic pressure and contractility were linearly correlated with the plasma concentrations (r=0.8−0.9,p〈0.001). The activity of prenalterol was also tested in the same volunteers after blockade of β-receptors with oxprenolol 80 mg. Under these conditions, oral doses of 25, 50 and 100 mg produced effects similar to or slightly less marked than those recorded after doses ten times lower in the absence of β-blockade. In a further 10 healthy volunteers, in whom tolerance to prenalterol was studied by repeated administration for 10 days of 5 mg four times daily, no change in blood chemistry, haematological parameters or urine values was found. The positive inotropic effect of a single oral dose of prenalterol 5 mg was also demonstrated by reference to the systolic time-intervals and the echocardiogram, in six patients with chronic heart failure, five of whom were digitalized. Prenalterol did not give rise to premature concentrations or other arrhythmias. The only untoward effect definitely attributable to the drug was palpitation, which was dose-related and as a rule was not unduly distressing; in one volunteer, however, the palpitations were unbearable. Prenalterol is a cardiostimulant agent with no direct effect on the peripheral circulation. On the basis of its pharmacological activity, it might well be of therapeutic benefit in all conditions in which an improvement in the pumping efficiency of the heart is required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636789
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  • 32
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 407-414 
    Details
    ISSN: 1432-1041
    Keywords: ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC] 0 ∞ after rectal administration of a suppository showed the minimum significant difference (p〈0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636794
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  • 33
    Electronic Resource
    Electronic Resource
    Inhibition by idrocilamide of the disposition of caffeine (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 37-43 
    Details
    ISSN: 1432-1041
    Keywords: caffeine ; idrocilamide ; xanthine derivatives ; inhibition of metabolism ; neuropsychiatric side effects ; pharmacokinetics ; healthy man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of caffeine are greatly altered by concomitant administration of idrocilamide. In four healthy volunteers id rocilamide inhibited the biotransformation of caffeine and increased its half-life nine times. The untoward neuropsychiatric effects of idrocilamide are the consequence of abnormal accumulation of caffeine in regular consumers of caffeine-containing foods and beverages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561675
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  • 34
    Electronic Resource
    Electronic Resource
    Altered prazosin pharmacokinetics in congestive heart failure (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 425-428 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; congestive heart failure ; pharmacokinetics ; oral dose ; comparison with healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of prazosin (Minipress®) were studied in nine patients with NYHA Class 3 or 4 congestive heart failure and in five healthy controls. After a single 5 mg oral dose, plasma concentrations of prazosin, as reflected in the area under the plasma concentration-time curve (AUC) and prazosin plasma half-life, were approximately double in the patients in comparison to the control group. Reduction in hepatic blood flow, altered gastrointestinal absorption of the drug or diminished intrinsic hepatic metabolic activity in the patient group may have contributed to the observed changes in prazosin disposition. The finding of higher prazosin plasma concentrations in patients with refractory heart failure demonstrates the need for close monitoring of these individuals following administration of the drug in the treatment of chronic congestive heart failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570159
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  • 35
    Electronic Resource
    Electronic Resource
    Placental transfer of pethidine and norpethidine and their pharmacokinetics in the newborn (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 25-30 
    Details
    ISSN: 1432-1041
    Keywords: pethidine ; norpethidine ; placental transfer ; pharmacokinetics ; newborns
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The literature data available on pethidine and norpethidine kinetics in women in labour and in their newborns is reviewed and compared with recent personal observations. In pregnant women the apparent blood half-life of pethidine is not different from that in healthy controls, however, apparent volume of distribution and total body clearance are reduced. Norpethidine blood levels are measurable after 10–20 min and tend to increase with time. The amount of drug transferred to the foetus is clearly linked to the dose administered to the mother, the dosing-delivery interval and to the metabolic capability of the mother. An equilibrium between maternal and umbilical venous blood is reached 2–3 h after dosing for pethidine and later for norpethidine. In the neonate, the apparent pethidine half-life is 2 to 7 times longer than in adults with values ranging from 7 to 32 h. Norpethidine is actively formed in the newborn with peak blood levels at 12–36 h and an apparent blood half-life of 20–36 h. At the doses usually recommended blood concentrations at birth are frequently higher than those required for analgesia and close to or within toxic ranges. An effort toward a more individualized dosage as well as toward a better understanding of the possible role of norpethidine with regard to adverse effects is needed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561475
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  • 36
    Electronic Resource
    Electronic Resource
    Disposition and pharmacodynamics of diuretics and antihypertensive agents in renal disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 109-116 
    Details
    ISSN: 1432-1041
    Keywords: diuretics ; antihypertensive agents ; renal disease ; dispositon ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic actions and disposition of diuretic and antihypertensive agents may be significantly modified in subjects with renal disease. Most studies on this question have dealt with alterations in the elimination kinetics of these drugs and, while they generate descriptive data, minimal insight about changes in dose-response relationships or mechanisms of drug action are provided by such investigations. Several basic principles which may serve as useful guidelines in determining how renal failure will influence the response to drugs have been considered. They include the following: degree of renal malfunction, intrinsic toxicity of the drug, alternative pathways for drug metabolism and elimination, elimination pharmacokinetics and dose-response characteristics. Several classes of diuretic agents (thiazides, furosemide) and antihypertensive drugs (hydralazine, methyldopa, propranolol, prazosin, and clonidine) have been used as models to define how basic knowledge of renal and non-renal pathways for elimination of drugs and their pharmacodynamic actions may assist in establishing rational therapeutic regimens for these agents in patients with renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561487
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  • 37
    Electronic Resource
    Electronic Resource
    Bromocriptine concentration in saliva and plasma after long-term treatment of patients with Parkinson's disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 171-174 
    Details
    ISSN: 1432-1041
    Keywords: bromocriptine ; Parkinson's disease ; plasma level ; salivary level ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salivary and plasma concentrations of bromocriptine (BCT), a dopamine agonist, were measured by gas chromatography in four patients with Parkinson's disease. All the patients had been on mono-therapy with BCT for years, and during the 3 weeks prior to the investigation they received constant but individually different dosage regimens. Paired samples of pure, parotid, serous saliva and of blood were collected hourly during one eight hour dose interval. The concentrations of BCT in saliva were very low and there was a ten-fold range in the areas under the salivary and plasma concentration/time curves. It is concluded that in clinical practice measurement of BCT in saliva is not suitable for exact estimation of the plasma concentration of BCT. Using the measured salivary pH and the plasma BCT concentration, calculations based on the Henderson-Hasselbalch equation showed that the assumption of about 99% plasma protein binding of BCT best fited the observed concentrations of BCT in saliva.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561586
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  • 38
    Electronic Resource
    Electronic Resource
    Comparative in vitro effects and in vivo kinetics of antithyroid drugs (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 295-299 
    Details
    ISSN: 1432-1041
    Keywords: propylthiouraci ; propranolol ; carbimazole ; methimazole ; comparative activity ; pharmacokinetics ; bioactivation ; thyroid peroxidase inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The in vitro effects of equimolar concentrations (0.1, 0.33 and 1.0 mmol/l) of carbimazole, methimazole, propylthiouracil and propranolol on thyroid peroxidase activity were studied on thyroid tissue specimens obtained from euthyroid patients undergoing parathyroidectomy. In addition, the in vivo kinetics of methimazole following single dose administration (60 mg) of carbimazole and of methimazole itself were examined in 11 healthy volunteers using high-pressure liquid chromatography to measure serum methimazole. The in vitro studies were carried out at pH 6, to avoid alkaline hydrolysis of carbimazole to methimazole. Under these conditions, methimazole strongly inhibited thyroid peroxidase. Propylthiouracil had a less pronounced inhibitory effect, and carbimazole was almost and propranolol was entirely inactive. The in vivo kinetics of methimazole showed a large interindividual variation. Within individuals, there was no significant difference in the half-life or time to peak concentration of methimazole following administration of carbimazole and methimazole, respectively. However, the peak concentration and area under the curve of methimazole were significantly greater after administration of methimazole itself than after administration of carbimazole. Assuming similar bioavailability, this difference could be related to the difference in molecular weight between carbimazole and methimazole. It appears that, in man, methimazole is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimazole, and that carbimazole offers neither dynamic nor kinetic advantages over methimazole.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00625803
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  • 39
    Electronic Resource
    Electronic Resource
    Time course of blood pressure, pulse rate, plasma renin and metoprolol during treatment of hypertensive patients (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 321-328 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; pharmacokinetics ; plasma renin ; blood pressure effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p〈0.001) between the initial (after three doses) and final (after 〉90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558443
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  • 40
    Electronic Resource
    Electronic Resource
    Influence of dose on the pharmacokinetics of Cefadroxil (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 505-509 
    Details
    ISSN: 1432-1041
    Keywords: cefadroxil ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of Cefadroxil have been studied in a crossover study involving 20 experiments in four healthy volunteers (19–24 years), after oral administration of five individual doses of 250, 500, 750, 1000 and 1500 mg of the antibiotic in capsules to each person. Plasma and urine concentrations of the antibiotic were determined microbiologically by a plate diffusion method. The antibiotic followed an open, single-compartment kinetic model. The plasma half-life was not significantly influenced by dose; the average was 1.438±0.220 h. The percentage of the antibiotic excreted in urine, too, was not significantly affected by the dose, being close to 80% of the quantity originally administered within 24 h. The values of Cmax and (AUC) increased linearly with the administered dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874664
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  • 41
    Electronic Resource
    Electronic Resource
    Comparative bioavailability of disopyramide after multiple dosing with standard capsules and controlled-release tablets (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 209-213 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; bioavailability ; controlled-release tablets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of disopyramide following repeated administration of standard capsules and controlled-release tablets have been compared. Ten patients were randomized into two groups; Group I received disopyramide capsules 150 mg every 6 h for five days and subsequently disopyramide controlled-release tablets 300 mg every 12 h for further five days. Group II received the same preparations in the reverse order. There was a more rapid rise in disopyramide concentration after the capsules: the maximum of 10.7±0.6 µmol/l (mean ± SEM) was reached within 1.8±0.4 h as compared to 10.6±0.4 µmol/l within 4.0±0.3 h after the controlled-release tablets. No significant difference in the fluctuations in individual plasma concentrations during each dose interval at steady state were observed after ordinary capsules compared to controlled-release tablets. The extent of bioavailability was the same. Eight patients reported some side-effects during the capsule period and nine during the controlled-release tablet period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561902
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  • 42
    Electronic Resource
    Electronic Resource
    Systemic availability of orally administered L-dopa in the elderly Parkinsonian patient (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 215-221 
    Details
    ISSN: 1432-1041
    Keywords: L-dopa ; elderly ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous studies have suggested that the absorption of L-dopa in the elderly Parkinsonian patient might be unusually efficient. In the present investigation, the systemic availability of L-dopa was examined in 5 elderly Parkinsonian patients (mean age=77 years) and 6 young, healthy volunteers (mean age=26 years) following a single oral 300 mg dose of L-dopa. Quantitation of plasma levels of intact L-dopa was effected by ion-exchange column chromatography and spectrofluorimetry. The L-dopa plasma concentration-time profiles obtained confirmed the considerable intersubject variability in the absorption of L-dopa previously reported in the literature. Maximum plasma concentrations of L-dopa generally occurred within 60 min of administration of the dose. The existence of more than one plasma peak of L-dopa concentration was displayed in 45% of the subjects studied. This characteristic was not confined exclusively to either subject group. There was a significantly larger (P〈0.02) area under the plasma L-dopa concentration-time curve (AUC o ∞ ) in the elderly Parkinsonian patients (mean=234.69 µg · min/ml; SD=84.70) compared to the young, healthy volunteers (mean=82.33 µg · min/ml; SD=31.00). A significant (P〈0.01) correlation existed between AUC o ∞ and age (r=0.7970; n=11) among the subjects studied. The apparent elimination phase plasma half-life of L-dopa in the elderly Parkinsonian patients (mean=66.0 min; SD=11.1) was not significantly different to that observed in the young, healthy volunteers (mean=74.0 min; SD=18.1). These results suggest that there may be an age-related alteration to the disposition of orally administered L-dopa in the elderly Parkinsonian patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561903
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  • 43
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of intravenous and oral sulpiride in healthy human subjects (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 385-391 
    Details
    ISSN: 1432-1041
    Keywords: sulpiride ; pharmacokinetics ; serum clearance ; renal clearance ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72±0.66 l/kg and total systemic clearance was 415±84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7–7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determination of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70±9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310±91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15±5% of the dose, with a mean renal clearance of 223±47 ml/min. The bioavailability determined from combined plasma and urine data was only 27±9%. The low bioavailability was probably due to incomplete absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558453
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  • 44
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and dosage of digoxin in neonates and infants (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 69-74 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; neonates ; infants ; pharmacokinetics ; dosage schedules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary As a therapeutic principle, a disease should be treated with the lowest effective dose of a drug. Accumulating information indicates that satisfactory contractile response of the myocardium is produced in young paediatric patients by doses of digoxin below existing recommendations. In addition, toxicity appears to be more frequent in neonates and infants treated with digoxin than previously thought. Therefore, dose calculations have been performed, based on pharmacokinetic parameters, with the aim of reaching and maintaining an average serum concentration of the glycoside of 2 nmol/l. This level is common in infants (〉1 month of age) during digoxin maintenance therapy and its adequacy is well supported by experience from adult cardiac patients. The calculations show that although current dosage schedules maintain the desired digoxin serum level in infants, they are often excessive for digitalization purposes. In neonates, the prevailing schemes do not sufficiently consider the immature state of the eliminating organs. Overdigitalization could therefore easily occur and continue in these patients, particularly in the premature newborns. This is in agreement with toxicity reports in the literature. The calculated doses should be less hazardous by being better adapted to the eliminating capacity of the various paediatric age-groups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561481
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  • 45
    Electronic Resource
    Electronic Resource
    Effectiveness and pharmacokinetics of indomethacin in premature newborns with patent ductus arteriosus (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 83-88 
    Details
    ISSN: 1432-1041
    Keywords: patent ductus arteriosus ; indomethacin ; premature newborns ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A review of the published data on pharmacological closure of PDA in premature newborns shows that doses of 0.2 mg/kg indomethacin are less successful when given enterally (18 to 85% closure) than when given intravenously (88 to 90% closure). The elimination half-life is markedly prolonged in premature newborns compared to adults but there are wide differences between the patients and some discrepancies between mean values reported by various authors. The present study compares clinical and pharmacological results obtained in two groups of low birth weight infants with symptomatic PDA and treated with 0.2 mg/kg indomethacin: 7 patients treated enterally (group A) and 11 patients treated intravenously (group B). Permanent closure of the ductus was observed in 4 cases in group A and in 9 cases in group B. Transient closure was observed twice in each group. Of a total of 18 infants, 15 were saved (83%). One baby treated with indomethacin in spite of preexisting oliguria died from persistent anuria. Indomethacin plasma levels were measured by gas chromatography. The mean elimination half-life of the drug in group A (40.3±12.2 h) did not differ from that in group B (33.9±11.7 h). The apparent plasma half-life appears to be inversely correlated with gestational age (r=0.66,p〈0.05). No relationship between peak plasma levels and ductal closure was established, but a significant difference was found for area under the curve (0 to 24 h) between patients in whom a permanent closure was obtained and those in whom the closure was either transient or absent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561483
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  • 46
    Electronic Resource
    Electronic Resource
    Nortriptyline therapy in elderly patients: Dosage prediction after single dose pharmacokinetic study (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 147-150 
    Details
    ISSN: 1432-1041
    Keywords: antidepressant ; geriatric ; nortriptyline ; pharmacokinetics ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen depressed elderly patients in hospital (mean age 81 years) received a single oral dose of nortriptyline prior to commencing treatment with this drug. Plasma nortriptyline measurements after the single dose were used to calculate the plasma drug clearance and to predict the daily dose required for each patient to achieve a steady-state concentration within the suggested therapeutic range of 50–150 µg·l−1. Using these dosage regimes, the mean observed steady-state concentration showed a significant correlation with the predicted values (r=0.71, p〈0.002). All patients had steady-state concentrations within or very close to this suggested range (mean 106, range 38–157 µg·l−1). Use of the prediction test can prevent the development of toxic plasma concentrations and enhance the possibility of therapeutic success. Our findings suggest that a safe starting dose of nortriptyline for the elderly is 30 mg per day.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561582
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  • 47
    Electronic Resource
    Electronic Resource
    Effect of posture and sleep on pharmacokinetics (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 175-183 
    Details
    ISSN: 1432-1041
    Keywords: amoxycillin ; pharmacokinetics ; bedrest ; sleep ; ambulation ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of amoxycillin in normal male volunteers was studied during the states of bedrest, sleep and ambulation. The absorption and disposition of amoxycillin in ambulatory subjects was found to be comparable to that reported previously by other workers. Serum amoxycillin concentrations were found to be significantly greater during ambulation than during bedrest and sleep. The difference in serum levels resulted from an increased apparent total serum clearance and amoxycillin renal clearance during bedrest and sleep compared to ambulation. No significant differences in the clearance was found between the states of bedrest and sleep. The change in renal clearance of amoxycillin during ambulation was attributed to a diminished renal blood flow. Although the terminal half-life of amoxycillin did not differ significantly, the apparent volume of distribution appears to be much greater during bedrest and sleep than during ambulation. This difference could be explained pharmacokinetically using a two compartment model. No significant difference was found between the rates of absorption of amoxycillin as reflected by the lag time and time to peak serum amoxycillin. The actual values for these parameters would suggest, however, that the absorption of amoxycillin is faster during ambulation than in bedrest and that the absorption rate during sleep is slowest. The clinical implications of the effect of posture and sleep on the pharmacokinetics of amoxycillin are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561587
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  • 48
    Electronic Resource
    Electronic Resource
    Use of an (n, α) nuclear reaction to study the long-distance transport of boron in trifolium repens after foliar application (1980)
    Springer
    Planta 150 (1980), S. 197-205 
    Details
    ISSN: 1432-2048
    Keywords: Boron ; Foliar nutrition ; Nuclear reactions ; Transport (boron) ; Trifolium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The growth of white clover (Trifolium repens L.) is severely inhibited by boron starvation, but a foliar treatment with boric acid can transitorily alleviate the deficiency symptoms. The 10B(n ,α)7 Li nuclear reaction has been used to study boron transport in the plant after foliar application. More than 98% of the boron supplied remained at the point where it was applied to the leaves, and less than 2% was useful to the growth of the treated plant. This small “efficient” portion of boron was quite mobile. It was distributed to the different parts of the plant, then was transferred from the oldest parts to the newly formed leaves. Physiological and agronomical implications of these data are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00390826
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  • 49
    Electronic Resource
    Electronic Resource
    Symbols in pharmacokinetics (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 497-507 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; symbols ; notation ; nomenclature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To encourage uniformity in the presentation of pharmacokinetic data, a general nomenclature has been developed. The system has wide application. Flexibility is achieved through the use of general variables, constants, qualifying terms, and subscripts. Yet, through the use of implied terms, the symbols describing many common variables and constants are simple.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059548
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  • 50
    Electronic Resource
    Electronic Resource
    Identifiable pharmacokinetic models: The role of extra inputs and measurements (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 633-648 
    Details
    ISSN: 1573-8744
    Keywords: compartmental analysis ; dynamic response ; identification ; linear systems ; modeling ; parameter estimation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Single input, single output experiments can result in nonunique solutions for the rate constants of a linear compartmental model used to describe the pharmacokinetics. Where a finite number of solutions exists, a priori knowledge has to be used to distinguish between the solutions. Where there is an infinite number of solutions, assumptions have to be made about the values of some rate constants in order to obtain a unique solution for the others. This paper considers such experiments and determines whether either the addition of an extra input (simultaneously with the first input) or the taking of an extra measurement would result in a unique solution. It is found that perturbing a second input can be useful, but only if the perturbation is of different shape from the first input. Measurements of drug in urine and metabolite in plasma are generally not helpful in resolving identifiability of the drug dynamic model. If a radioactive tracer is used, though, the second measurement (for example, by externally scanning the radioactivity of the liver) can prove useful, but only if the gain of the measuring device is known.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060058
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  • 51
    Electronic Resource
    Electronic Resource
    Accumulation in the peripheral compartment of a linear two-compartment open model (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 99-104 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacological effects ; two-compartment model ; tissue accumulation ; aminoglycoside antibiotics ; gentamicin ; nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Accumulation factors for the peripheral compartment in a two-compartment open model are derived. These expressions are contrasted with some previously published statements concerning drug accumulation. The utility of the new indices of accumulation is illustrated by reference to studies of gentamicin tissue uptake and its proposed relation to nephrotoxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059451
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  • 52
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    Electronic Resource
    Pharmacokinetics of intravenously administered bumetanide in man (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 219-228 
    Details
    ISSN: 1573-8744
    Keywords: bumetanide ; diuretics ; pharmacokinetics ; three-compartment model ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Disposition of [ 14C] bumetanide administered intravenously to four healthy volunteers could be described by a triexponential equation. The mean half-lives associated with each exponent were 5.9 min, 46 min, and 3.1 hr, respectively. The largest fraction of dose was eliminated during the second phase; only 17% was eliminated during the last phase. The total plasma clearance averaged 228 ml/min, with renal clearance about one-half of this value. The recovery of unchanged bumetanide in urine over 2 days was 47% of the dose, while the total recovery of radioactivity in urine averaged 82% of dose. In plasma 93% of bumetanide was bound to proteins. Thus bumetanide is rapidly eliminated by both renal and nonrenal mechanisms. The elimination kinetics resembled those described for furosemide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059643
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  • 53
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of bretylium in man after intravenous administration (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 363-372 
    Details
    ISSN: 1573-8744
    Keywords: bretylium ; pharmacokinetics ; healthy subjects ; antiarrhythmic ; twocompartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetic profile of bretylium was studied in four normal male volunteers using a new sensitive EC-GC procedure for its quantitation in biological fluids. The plasma concentrations and urinary excretion rates following the constant i.v. infusion of a single 4mg/kg dose of bretylium tosylate declined biexponentially and the data were fitted to a two-compartment model with a renal and a nonrenal route of elimination. The drug had a mean half-life (t1/2β)of 7.8 hr and apparent volume of distribution (Vd,β)of 8.18 liters/kg. The renal clearance, which was 6 times that of the glomerular filtration rate, accounted for almost 84% of the total body clearance and correlated linearly with the subjects' creatinine clearance. The observed side effects of bretylium were mild and similar to those of other adrenergic blocking agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059384
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  • 54
    Electronic Resource
    Electronic Resource
    Influence of renal failure on the hepatic clearance of bufuralol in man (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 421-438 
    Details
    ISSN: 1573-8744
    Keywords: bufuralol ; renal failure ; pharmacokinetics ; metabolites ; renal clearance ; hepatic clearance ; first-pass metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The beta-blocking agent bufuralol is subject to first-pass metabolism and is eliminated from the body almost entirely by biotransformation. Its major metabolite in plasma (1′-hydroxy-bufuralol) is biologically active and may contribute to the pharmacological effect of the drug. The effect of renal failure on the behavior of the parent compound and three of its metabolites was studied by comparing their kinetics in normal volunteers and in patients with severe renal insufficiency. Bufuralol was given orally to all subjects (20 mg); some of the healthy volunteers also received the drug intravenously (5 mg). Renal failure was found to be associated with a marked increase of the areas under the plasma concentration-time curves of the parent compound, whereas its halflife of elimination was not markedly influenced. The behavior of 1′-hydroxy-bufuralol was consistent with a decreased renal clearance. The behavior of bufuralol in patients with renal failure was analyzed using the clearance approach. From this analysis it appears that the presystemic biotransformation of bufuralol is decreased in renal failure and that changes in systemic clearance are compensated in our patients by modifications of the volume of distribution, resulting in little net change in the halflife of elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059544
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    Electronic Resource
    Lithium pharmacokinetics: Single-dose experiments and analysis using a physiological model (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 439-461 
    Details
    ISSN: 1573-8744
    Keywords: lithium ; pharmacokinetics ; physiological parameters ; cellular transport ; three-compartment model ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The kinetics of lithium (Li +) distribution after a single dose was studied in healthy human subjects. Experiments were performed by simultaneously following changes of Li+ concentration in plasma, erythrocytes (RBC), and urine. The data were fitted by a simple but physiologically realistic model, so that extracted rate constants could be assigned to real body compartments and compared with independent measurements of cellular transport characteristics. The extracted rate constants were used to calculate steady-state cell-to-plasma Li+ ratios for RBC and for inaccessible cells (mainly muscle). In both cell types, the intracellular Li+ concentration is far below electrochemical equilibrium. This finding suggests that the Li+ countertransport efflux mechanism of RBC may be shared with muscle. We also present evidence for a circadian rhythm in Li+ excretion that parallels the daily cycle of Na+ and K+ excretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059545
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  • 56
    Electronic Resource
    Electronic Resource
    A pharmacokinetic model-independent approach for estimating dose required to give desired steady-state trough concentrations of drug in plasma (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 105-110 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; maintenance dose ; dose estimation ; multiple dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A maintenance dose designed to give a desired minimum concentration of drug in plasma at steady-state can be determined in a model-independent manner assuming that concentration-time data needed for the calculation are obtained after absorption and distribution are complete. Using a few concentration-time points obtained after the first dose, numerical values of β and Z, a parameter consisting of different pharmacokinetic parameters for different models, can be obtained. An administration interval (τ) can be chosen based on β. Using the values of β, Z, and τ, a maintenance dose is calculated. This approach will allow calculation of a maintenance dose when drug is present in plasma at the time the first monitored dose is given.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059452
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  • 57
    Electronic Resource
    Electronic Resource
    Heuristic modeling of drug delivery to malignant brain tumors (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 257-296 
    Details
    ISSN: 1573-8744
    Keywords: chemotherapy ; pharmacokinetics ; brain tumors ; modeling ; solid tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract It is apparent that chemotherapy against malignant brain tumors is generally ineffective. While some agents are more effective than others, none appreciably alters the clinical course of and the poor prognosis for patients with brain tumors. Even though new and more effective agents are being or will be developed, chemotherapy depends as much on the delivery of drug as it does on the drug used. Therefore, we have defined factors that we believe are of primary importance in drug delivery to brain tumors, and, using computer simulation, we have modeled the effects of these factors. In this article we discuss (a) the extent of the “breakdown” in the blood-brain barrier (BBB) that accompanies the development of malignant tumors in the brain, (b) factors that influence drug transport from tumor capillaries to tumor cells at varying distances from the capillaries, (c) the problems inherent in drug delivery from a well-vascularized tumor outward to normal brain tissue that might harbor malignant cells but that does not have leaky vessels (i.e., normal BBB), and (d) the difficulties in drug delivery from a well-perfused, highly permeable outer tumor shell to a central, poorly perfused tumor core.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059646
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  • 58
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    Electronic Resource
    Large-scale preparation of a lectin from sunn hemp seeds (Crotalaria juncea) (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 79-88 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A procedure for large-scale preparation of a lectin from Crotalaria juncea seeds is described. The method involve fractionation by pH- and ammonium sulfate precipitation followed by biospecific affinity chromatography. The adsorbent used for the affinity chromatography was prepared by coupling galactose to Sepharose 6B activated with divinylsulfone. A comparison of different apparatus and techniques involved in the preparation is discussed. The yield and quality of the lectin prepared at a large scale were comparable with laboratory-scale preparation. From 50 kg Crotalaria juncea beans, 14.4 g Crotalaria lectin were obtained.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220107
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  • 59
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    Electronic Resource
    Model of growth and ergot alkaloid production by Claviceps purpurea (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 255-270 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A growth model for Claviceps purpurea in submerged batch culture is presented. In developing the model, the basic principles of the growth and the morphological properties of C. purpurea are considered. The growth of C. purpurea is assumed to occur in a three-step manner; the first step involves the assimilation and the growth of cells; the second one involves cell division, and the third one involves transformation of the mature cells to a state where they have no ability to divide but do have the ability to produce ergot alkaloids and then they gradually die. Inorganic phosphate is assumed to be the limiting substrate for the first and the second steps in conditions of carbon source being in excess. The model constants are determined by model simulation and graphical searching techniques to find the minimum value of the absolute difference between the experimental and the simulated curves for biomass, alkaloids, and sucrose.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220202
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  • 60
    Electronic Resource
    Electronic Resource
    Immobilization of β-galactosidase and other enzymes onto p-amino-carbanilated cellulose derivatives (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 311-321 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: β-Galactosidase and other enzymes were immobilized on p-amino-carbanilated derivatives of cellulose and methylol cellulose using the diazo method and through glutaraldehyde. The optimum conditions for coupling cellulose tri-(p-amino-carbanilate) (CTAC) to β-galactosidase were established. The diazo coupling method with CTAC gave greater activity than with glutaraldehyde when coupled to β-galactosidase (Escherichia coli). The stability of the CTAC-β-galactosidase system was examined. The disubstituted p-amino-carbanilate derivative (CDAC) gave a lower activity, whereas the methylol analog (MCTAC) gave slightly greater activity. The CTAC was also used to immobilize glucose oxidase, trypsin, pepsin, and papain.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220206
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  • 61
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    Electronic Resource
    Hydrophobic chromatography of β-galactosidase (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 377-399 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The hydrophobic interaction of β-galactosidase with Sepharose 4B substituted with 3,3′-diaminodipropylamine was studied in both batch and column experiments. The equilibrium and the binding rate constants were determined for different phosphate buffer concentrations. The equilibrium constants exhibit a hysteresis effect, i.e., desorption constants are less than adsorption constants, and the higher the ionic strength to start the desorption, the larger the effect. The rate data are not satisfactorily described by a simple reversible first-order model. The column chromatographic data are semiquantitatively described by a local equilibrium theory without axial dispersion or intraparticle diffusion.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220211
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  • 62
    Electronic Resource
    Electronic Resource
    Enzyme formation during solid-substrate fermentation in rotating vessels (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 411-420 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Aspergillus awamori NRRL 4869 was cultured on the solid substrate, wheat bran, in a modified Rollacell apparatus to produce α-galactosidase and invertase. The swivel cap on the elongated bottle permits the introduction of air while the bottle rotates. Parameters of air flow rate (0.05-0.2 liter/kg/min), rpm (0.15-15 rpm), and weight of solids (150 and 300 g) were varied. At low air flow rates (0.05 liter/kg solid/min), α-galactosidase production was minimal independent of the rotation rate. At 0.15 rpm and 0.2 liter/kg solids/min air flow rate, invertase production ceased after five days; whereas α-galactosidase production continued. The modified Rollacell can be a useful apparatus for studying solid-substrate cultures.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220213
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  • 63
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    Electronic Resource
    Temperature and pH dependence of mold α-galactosidase (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 505-518 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The effect of temperature and pH on kinetic behavior of α-galactosidase of Mortierella vinacea was investigated on the hydrolysis of p-nitrophenyl-α-D-galactopyranoside (PNPG). A very unusual kinetic behavior was observed for the soluble α-galactosidase i.e., substrate inhibition diminished gradually with increasing temperature or near the neutral pH range, and the kinetics approached the ordinary Michaelis-Menten (MM) type. On the other hand, with decreasing temperature or in acidic pH range, substrate inhibition was accelerated. Therefore, Arrhenius plots based on the initial reaction rate did not give straight lines. Furthermore, the slope in the Arrhenius plot changed with substrate concentration, which would make the determination of a characteristic value using conventional methods meaningless. However, the Arrhenius plots of individual kinetic parameters in the rate equation resulted in straight lines in the temperature range 15 to 50°C. From this, the drastic change in kinetic behavior could be explained in connection with the temperature and pH dependence of kinetic parameters in the model. For mold pellets (whole-cell enzyme), however, the influence of temperature and pH was less apparent than that of soluble enzyme because of the limitation in intraparticle diffusion. By using the rate equation that was determined for soluble enzyme and the theoretically derived effectiveness factor, the overall reaction rate for mold pellets at various temperature and pH could be predicted to some extent.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220304
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  • 64
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    Electronic Resource
    Optimization of the production of progesterone 11α-hydroxylase by Rhizopus nigricans (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 555-570 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The progesterone 11α-hydroxylase of Rhizopus nigricans ATCC 6227b is an inducible enzyme system that is primarily induced by its substrate progesterone. Maximum induction was found at a progesterone concentration of 0.5 g/liter or above. Oxygen is the other substrate for the hydroxylation and this was found to have a major effect on the amounts of hydroxylase synthesized. Optimum induction of the hydroxylase in a fermentation with a 3.1 m/sec impeller tip speed was found to occur at a dissolved oxygen tension (DOT) of 10% of air saturation. The agitation rate also effects the amount of hydroxylase synthesized with an apparent maximum at 3.1 m/sec impeller tip speed. The DOT for a maximum hydroxylation rate was much higher than for enzyme synthesis so that it was preferable to increase the DOT after induction was completed.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220308
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  • 65
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    Electronic Resource
    Growth of yeast on n-alkanes. II. Batch experiments (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 615-637 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: In this paper the results of the Monte Carlo simulations as described in an earlier paper are compared with those of batch experiments. A number of batch experiments were carried out at a low inoculation rate so that only a fraction of the oil drops were inoculated. Under these conditions the effect of the segregation of the oil phase is more clearly demonstrated. Special attention is paid to the preparation of actively growing yeast cells with which the cultures is inoculated. Also a method is developed to estimate the amount of actively growing cells with which the culture is inoculated. The other parameters necessary for the Monte Carlo simulation are measured in separate experiments: the maximum growth rate of the cells, oil drop size, and the drop parameters. Finally the growth curves (measured in the batch experiments) are compared with those calculated with the Monte Carlo procedure. A good agreement is found.
    Additional Material: 17 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220311
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  • 66
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    Electronic Resource
    Mechanism of the enzymatic hydrolysis of cellulose: Effects of major structural features of cellulose on enzymatic hydrolysis (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 177-199 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The susceptibility of cellulose to enzymatic hydrolysis is affected by the structural features of cellulosic materials. It has been suggested that the crystallinity and surface area of cellulose fibers are the most important structural features in this regard. This study investigated in depth the relative effects of these two structural features upon the enzymatic hydrolysis of cellulose and the change of the structural parameters of cellulose during the course of hydrolysis. It was found that the hydrolysis rate is mainly dependent upon the fine structural order of cellulose which can best be represented by the crystallinity rather than the simple surface area. Monitoring the changes in the structural parameters during the course of reaction showed that surface area is not a major limiting factor that slows hydrolysis in its late stages as has been suggested. This information concerning structural features is used to elucidate the mode of action of cellulase.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220113
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  • 67
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    Simple device for the spectrophotometric assay of immobilized enzymesThis work was presented at the September 30, 1977 meeting of the New Mexico Academy of Science at Silver City, New Mexico. (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 227-229 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220117
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  • 68
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    Electronic Resource
    Reactivation of “irreversibly” denaturated enzymes (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 247-251 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220121
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  • 69
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    Growth energetics in the production of bacterial single cell protein from Methanol (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 353-362 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Bacteria grown on methanol exhibit a poor efficiency of energy conservation, which is mainly due to the low P/O ratio of 1 associated with methanol oxidation. Thermodynamic considerations indicate that a P/O ratio of at least 2 is possible for this step in substrate oxidation. This low efficiency of energy conservation is reflected in the yield values on methanol, which are very important in the consideration of biomass production from methanol. Unfortunately in continuous culture there is no obvious way to select for organisms with a greater efficiency of energy conservation.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220209
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  • 70
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    Electronic Resource
    Growth and anthocyanin production by carrot suspension cultures grown under chemostat conditions with phosphate as the limiting nutrient (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 337-352 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Chemostat cultures of carrot suspension cultures, where growth was limited by the concentration of phosphate in the input medium, were achieved by replacing a fixed proportion of the culture with fresh medium at daily intervals. In the range 0.05-0.30mM phosphate in the input medium and at a specific growth rate of 0.357 days-1, steady-state culture density but not anthocyanin in the cells was strictly proportional to the input phosphate concentration with no intercept. At a phosphate concentration of 0.10mM and growth rates from 0.105 to 0.430 days-1, the steady-state culture density could not be described by Monod's model of chemostat cultures, but could be described by Nyholm's model. The steady-state levels of anthocyanin were not strictly proportional to the steady-state biomass under all conditions, showing that anthocyanin production is not completely growth associated.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220208
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  • 71
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    Growth kinetics under adenine-limiting conditions of Bacillus subtilis KYA 741, an adenine-requiring strain (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 401-410 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The growth kinetics of Bacillus subtilis KYA 741, an adenine-requiring strain, was investigated under adenine-limiting conditions. The concentration of adenine (the limiting substrate for cell growth) in the culture filtrate remained constant during the stationary phase. In this phase, DNA turnover was active and the DNA content per cell was constant throughout the cultivation period. When cells were transferred to medium without adenine, the cell concentration began to decrease immediately and then reached a constant level due to the supply of adenine from lysing to growing cells. The rates of degradation of cells and DNA were both found to be 0.2 hr-1. An equation for cell growth in this pseudostationary phase was obtained by combining Contois' equation, in which the apparent saturation constant was a function of the cell concentration, with a term for cell degradation. This equation satisfactorily expressed the feature of cell growth and adenine consumption by B. subtilis KYA 741 under adenine-limiting conditions.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220212
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  • 72
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    Enzymatic biosynthesis of cephalexin (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1237-1247 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The reaction kinetics of the enzymatic of cephalexin from 7-aminodea-cetoxy cephalosporanic acid and phenylglycine methylester was studied using the synthesizing enzyme obtained from Xanthomonas citri. The activation energy, Km value for 7-aminodeacetoxy cephalosporanic acid and phenylglycine methylester, and Ki value for phenylglycine methylester were determined as 8.63 kcal/mol, 3.7mM, 14.5mM, and 70mM, respectively. The enzyme was found to be constitutive and susceptible to deactivation.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220610
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  • 73
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    Introduction (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1295-1296 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220702
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  • 74
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    Estimation of diffusion coefficients of proteins (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 947-955 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A correlation for estimating the diffusion coefficients of protein molecules is presented. The correlation is based upon literature values of the protein diffusion coefficients and molal volumes for 143 proteins. The correlation can be used for the estimation of diffusion coefficients using only molecular weight. Accuracy is such that a linear regression on 301 proteins showed 75% of the diffusion coefficients estimated fell within 20% of the experimental values. The relationship between this correlation, the Stokes-Einstein equation, and the Wilke-Chang correlation is discussed.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220504
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  • 75
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    Surface aeration in a small, agitated, and sparged vessel (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 981-993 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: In a recent publication, a technique was outlined for measuring surface aeration rates in an agitated vessels while sparging, and it was shown that surface aeration rates fall rapidly with increasing sparge rates. That work was conducted in a 0.61 m diam vessels. The work reported here was done in a small vessel (0.22 m diam) where surface aeration has been reported to be of particular significance. In general, the results obtained in the small vessel confirmed those in the large one and in addition were generally in good agreement with those recently published elsewhere for an almost identical geometry. For typical practical power inputs and sparge rates, the rate of surface aeration was never more than 20% of the sparge rate and generally less than 5%. These results indicate that surface aeration is of considerably less importance than has generally been believed following the findings of workers who estimated its effect by comparing KLa values under unsparged conditions with those when sparging.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220507
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  • 76
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    Enhancement of cellulose accessibility and enzymatic hydrolysis by simultaneous wet milling (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1025-1036 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: It has been shown that the rate of enzymatic saccharification of cellulosic materials including “pure” cellulose (Whatman CF-11 cellulose), newsprint, lignocellulose (prehydrolyzed to remove hemicelluloses), and wood can be substantially increased by simultaneous wet milling. An enhanced hydrolysis rate was sustained above that observed for ball milling: providing a more extensive saccharification. The cellulosic substrates were wet milled with a variety of grinding elements, such as sand, glass beads, and stainless-steel beads, agitated in a shaker bath. Simultaneous hydrolysis was achieved with a 2% substrate slurry in a 0.1M acetate buffer at 45°C and pH 5. The effectiveness of this process was dependent upon the lignified matrix of the cellulose microfibrils, the grinding elements, and the oscillation frequency of the shaker bath. Wet milling “pure” cellulose for 48 hr, with 3.5 mm glass beads and 200 oscillations/min (opm), yielded 1031 mg reducing sugar/g substrates (93% saccharification) as compared to 483 mg (44%) for the ball-milled sample and 253 mg (23%) for the unmilled material. With the lignified substrates stainless-steel beads (3.5 mm) were more effective than glass. For lignocellulose 529 mg sugar/g substrate (93% saccharification) could be obtained by wet milling with cellulase for 24 hr. This was about three times greater than that of the ball milled (169 mg, 30%) and 10 times greater than that of the unmilled (52 mg, 9%) substrates. The method was also effective for wood particles (60 mesh) giving 143 mg sugar/g wood (approximately 38% saccharification) in 48 hr, whereas the ball-milled sample gave only 79 mg (21%) and the unmlilled substrate 38 mg (10%). These observations can be explained on the basis of the current crystalline theory for the morphology of the cellulosic microfibrils. The advantage of wet milling and simultaneous hydrolysis apparently depends on a continuous generation of accessible sites and sustained rapid hydrolysis rate as the saccharification proceeds, where in the pretreated substrates the hydrolysis rate slow down as the active sites are reduced.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220511
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  • 77
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    Masthead (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980) 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220601
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  • 78
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    Purification and immobilization of Aspergillus niger β-xylosidase (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1127-1142 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: β-Xylosidase from a commercial Aspergillus niger preparation was purified by differential ammonium sulfate precipitation and either gel permeation or cation exchange chromatography, giving 16-fold purification in 32% yield for the first technique or 27-fold purification in 19% yield for the second. The second method in addition almost completely removed interfering β-glucosidase activity. Enzymes prepared by this method was immobilized to 10 different carriers, but only when it was bound to alumina with TiCl4 and to alkylamine porous silica with glutaraldehyde were substantial efficiencies and stabilities achieved. With alumina, the variation of activation procedure, amount of β-xylosidase offered, and activation solution composition yielded maximum activities of over 40 U/g with approximately 70% immobilization efficiency. Variation of binding pH and incubation time led to a maximum immobilized activity of 1.3 U/g with 78% immobilization efficiency on silica.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220603
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  • 79
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    Immobilized yeast cells with methanol oxidase activity: Preparation and enzymatic properties (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1155-1173 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Cells form the yeast Hansenula polymorpha (ATCC 26012) were successfully immobilized by entrapment in a polyacrylamide gel. The resulting gel showed high methanol oxidase activity especially after treatment with a detergent (CTAB). The enzymatic properties of the gel-entrapped cell were not very different from that of the soluble enzyme except that no inhibition was observed at high methanol concentration. In continuous reactors, the gel-entrapped cells showed a much higher stability than other enzyme preparations. The inactivation mechanism was investigated and proved to be the oxidation of essential SH group(s) of the methanol oxidase molecule by hydrogen peroxide. Treatment with β-mercaptoethanol prevented inactivation or regenerated activity.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220605
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  • 80
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    Polymethylglutamate as a new matrix for covalently immobilized enzymes: Preparation and properties of urease and uricase (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1225-1235 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Polymethylglutamate (PMG), a synthetic polypeptide, was used as a new carrier to immobilize urease (EC 3.5.1.5) and uricase (EC 1.7.3.3) by the azide method. The enzymes could be immobilized onto PMG in various forms, such as film, fiber, coating on various beads, and a silicon tube. The retained activities of the immobilized enzymes were excellent (more than 95%), therefore it was possible to immobilized almost all activities of the enzymes added in the coupling mixtures. Heat stabilities of the resulting immobilized enzymes were markedly improved, while the optimal pH and Km values remained almost unchanged. The urease immobilized on the PMG-coated glass beads packed in a column, was found to retain its activity more than 80% of the initial value, even after the occasional use for a year. In view of the improved retained activities and stabilities of the immobilized enzymes, PMG may therefore be a very versatile matrix for the immobilized enzymes.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220609
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  • 81
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    Microcalorimetry of microorganism metabolism of monosaccharides and simple aromatic compounds (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1249-1269 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Heat conduction solution enable rapid determination of the heats of aerobic and anaerobic metabolism of substrate by microorganisms. Aliquots of 1.0 ml cell suspension, 5 × 109 cell/ml, were mixed with a few dozen nmol substrate contained in 0.5 ml, under a controlled atmosphere of air, O2, or N2. At these substrate concentration, with adapted microorganisms, metabolism and its heat generation are usually complete within 300 to 600 sec. The raw data yield ΔHapp values. The ΔHapp were determined in the range 0.001 to 0.010% substrate, and extrapolated (limit substrate concentration →0), to yield Δ0H̄, the limiting differential molar heat of metabolism. The Δ0H̄ values express the heat generated when there is rapid metabolism but little new growth, minimal contribution by H+ transfer from metabolites, and maintenance of aerobicity or anaerobicity as specified. Escherichiacoli B/5 was used for aerobic and anaerobic combustion of eight sugars. Pseudomonas multivorans, and an Acinetobacter, strain B-1, were used for aerobic metabolism of benzene, toluene, naphthalene, and a methylnaphthalene. The larger heats of combustion of the hydrocarbons enable the use of aqueous solutions of hydrocarbons well below their solubility limits. The quotient Δ0H̄/n (n = atoms carbon/molecule substrate) varies from (-)36 to (-)67 kcal/mol carbon for the sugars. The most reduced sugar yields the largest exothermic heats. The quotient varies from (-)27 to (-)81 kcal/mol carbon for the aromatic hydrocarbons. Comparison of the calorimetric heats of metabolism of those from total aerobic combustion in aquo (where available) give measure of the efficiencies with which the heat contents of the aqueous substrate are used by the bacteria.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220611
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  • 82
    Electronic Resource
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    Bacillus sphaericus for the control of mosquitoes (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1335-1355 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: From 1972 to 1977 a large laboratory effort was devoted to determining data on efficacy, safety, environmental impact (on nontarget organisms), and some preliminary field work using several isolates of Bacillus sphaericus. The B. sphaericus strains were found to be specific in their mosquito larvicidal activity, not causing mammalian toxicity nor apparent perturbation of the environment. During this period several fermentation and industrialization problems were investigated so that by 1978, using new strains and cultures, it was possible to have prepared kilogram amounts of an active dry stable powder, of strain 1593, for field evaluation. These field evolution. These field evaluations are presently still in progress. Control has been seen particularly against Culex, Anopheles, and Psorophora species, with some what less control aganst Aedes species. Unlike the agriculturally oriented Bacillus thuringiensis candidates, B. sphaericus bacterial cell, which is digested in the larval midgut (within a peritrophic membrane), releasing a toxin as early as 15 min after ingestion. Subsequent death of the larva ensues. Recent evidence suggests that applied B. sphaericus powder will survive in aquatic situations (ditches, ponds, and tree holes) for at least nine month. Comparisons of the B. sphaeicus strains with recently isolated strains of B. thuringiensis (var. israelensis), the latter being particularly active against Aedes species, indicates that they may be useful complements of each other in overall mosquito control strategies. The recent isolation of several new strains of B. thuringiensis, from WHO-CCBC accessions from Roumania, indicate that although the B. thuringiensis isolate is a rare event when compared to the occurrence of B. sphaericus isolates (they usually occur together in accessions from which B. thuringiensis is isolated), several new useful strains of B. thuringiensis should be anticipated. The longevity of the B. thuringiensis strains in the wild has not yet been investigated.
    Additional Material: 11 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220705
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  • 83
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    Partial acid hydrolysis of cellulosic materials as a pretreatment for enzymatic hydrolysis (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1449-1463 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Partial acid hydrolysis was studied as a per treatment to enhance enzymatic hydrolysis, such a pretreatment was carried out in a continuous flow reactor on oak corn Stover, newsprint, and Solka Floc at temperatures ranging from 160 to 220°C, acid concentration ranging from 0 to 1.2%, and a fixed treatment time of 0.22 min. The resulting slurries and solids were than hydrolyzed with Trichoderma ressei QM 9414 cellulase at 50°C for 48 hr. For all substrates except Solka Floc, increased glucose yields were achieved during enzymatic hydrolysis of the pretreated materials as compared to hydrolysis of the original substrate. In several cases, after pretreatment, 100° of the potential glucose content of the substrate was converted to glucose after 24hr of enzymatic hydrolysis. It is felt that the increased glucose yields achieved after this pretreatment are due to acid's removal of hemicellulose, reduced degree of polymerization, and possibly due to a change in the crystal structure of the cellulose.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220711
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  • 84
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    Enzymatic modification of vegetable protein: Mechanism, kinetics, and production of soluble and partially soluble protein in a batch reactor (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1543-1565 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Enzymatic hydrolysis of insoluble soybean protein by a protease enzyme produced by Penicillium duponti K 1104, was investigated in a batch reactor. The reaction conditions were 30-55°C and pH 3.4-3.7. The mechanism of solubilization of the insoluble protein by the Penicillium duponti enzyme was deduced from a series of experiments. Kinetic models were developed that involved adsorption followed by peptic digestion of protein, inhibition of low-molecular-weight peptides, and enzyme deactivation. The uncoupled kinetic parameters were estimated using the Marquardt nonlinear parameter estimation algorithm. A bang-bang production of soluble and partially soluble protein is suggested for higher productivity. The essential amino acids pattern of the enzyme-Hydrolyzed soy protein was comparable with the unhydrolyzed protein isolate. Aggregation of the soluble protein for an extended time was observable. The low-molecular-weight soluble protein was incorporated into noncarbonated beverages. The amount of protein that could be incorporated into a can of 355 ml noncarbonated beverage, without observable changes in the optical density and also aggregation of the protein, was 2.5 g soluble protein. Beverages with caramel color showed excessive decrease in optical density and precipitation. The kinetics and diffusion in a multipore immobilized-enzyme recycle reactor will be considered in part II of this series.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220804
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  • 85
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    Energy requirements for the vacuferm processPrepared for the U. S. Department of Energy under Contract No. W-7405-ENG-48. (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1749-1751 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220815
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  • 86
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    Criteria for multiple steady states in immobilized-enzyme systemsNCL communication No. 2512. (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 1759-1765 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220817
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  • 87
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    Simple model for the energetics of growth on substrates with different degrees of reduction (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 33-53 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A simple model is developed for the energy transformation in growing microbial systems. The model is based on a linear equation for ATP consumption in the processes of growth and maintenance. A combination of this equation with macroscopic balances for the various components, the systems exchanges with the environment, and application of the concepts of the elementary balance allow the derivation of linear equations for the exchange of substrate, oxygen, and carbon dioxide with the environment. For growth on one sole carbon and energy source the model allows the definition of a critical substrate yield are expected and below which is decreasing substrate yield and energy supply growth limitation are expected. This restriction can be interpreted in a variety of other ways. It supplies a rationale for non-energy-production-coupled transfer of hydrogen to oxygen or wasteful expenditure of ATP in growth on highly reduced substrates. It also allows the formulation of a limit to the maximum yield on oxygen that can never be exceeded in growth on highly reduced substrates.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220104
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  • 88
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    Dynamic aspects of radiorespirometry during the cell cycle of Candida utilis: Some observations in phased culture under carbon-, nitrogen-, and phosphorus-limited growthNRCC NO. 17791. (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 137-156 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Many changes that occur in a cell during the cell cycle can be demonstrated in synchronous cultures and can reveal dimensions of cell metabolism not attainable by the study of balanced growth of asynchronous populations in batch cultures or the steady state in chemostat cultures. The release of 14CO2 from specifically labeled glucose by phased (continuously synchronized) cultures follows a characteristic pattern (profile) that depends upon the stage in the cell cycle and the period of labeling used. Successive profiles throughout a cycle showed differences that were altered under different nutrient-limiting growth conditions. Profiles obtained with glucose-1-14C, glucose-2-14C, glucose-3,4-14C, and glucose-6-14C and phased cells of Candida utilis under N-, P-, and C-limited growth demonstrated the variable character of the metabolic activity that occurred in the cells while contour changes within the profiles across the cycle indicated possible correlations with activities of the hexose monophosphate, Embden-Meyerhof-Parnas, and tricarboxylic acid cycle pathways during the cell cycle. The basis of these changes and their use as elementary parameters for study of problems of physiological changes in vivo are considered.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220111
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  • 89
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    Experimental technique for multilayer enzyme immobilization (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 215-219 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220115
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  • 90
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    Response of a continuous culture of saccharomyces cerevisiae to variation of temperature (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 231-235 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220118
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  • 91
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    Masthead (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980) 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220201
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  • 92
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    Electronic Resource
    Enzyme electrode for phenol (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 299-310 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: An enzyme electrode is described for quantitative determination of phenol at micromolar concentrations. Immobilized phenol hydroxylase is attached to the surface of a Clark oxygen electrode. The Maximum rate of oxygen consumption is linearly dependent on phenol concentration over the 0.5-50μM range. The electrode can be used for at least 150 assays without an activity loss. Readout is very rapid - within 30 sec of sample addition. The electrode response is independent of pH between pH 6.5 and 9.5. The response increases linearly with temperature in the interval 10-40°C. It is necessary to incubate the enzyme electrode in a buffer containing NADPH for a few minutes before the addition of sample. This is to make the electrode response independent of the diffusion rate of this cosubstrate. This and other diffusional effects on the performance of the phenol electrode are discussed.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220205
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  • 93
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    Stability of the Cellulase of Trichoderma reesei under use conditions (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 323-335 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Enzyme stability studies have been reinvestigated under the conditions used for cellulose hydrolysis (pH 4.8, 50°C, 24 hr). The cellobiohydrolase (CBH) component as measured on Avicel is less stable than other enzymes of the cellulase complex, and is 60% inactivated by merthiolate (and other Hg compounds) under the above conditions. Endo-β-1,4-glucanase is much more stable, and more resistant to merthiolate and other compounds. Under unshaken conditions the Avicelase of the Rutgers strain C 30 shows greater stability to heat than that of other available strains. Biocides must be selected not only for their ability to prevent contamination, but also for their compatibility with cellulases. Tetracycline and chlortetracycline are inexpensive, effective in very low concentrations, have no harmful effect on the enzymes, and are compatible with the yeasts that subsequently grow on the sugar solutions to produce alcohol. Attempts have been made to stabilize the enzymes by chemical modification in such a way as to maintain their solubility. Glutaraldehyde treatment greatly increased the enzyme size, lowered the pI values, and gave a slight shift in the pH activity curve. There was, unfortunately, no increase in enzyme stability, and the activity of enzymes on solid celluloses was adversely affected. Shaking greatly reduced the hydrolysis of Avicel by Trichoderma reesei C 30 enzyme. The adverse effect was accompanied by a decrease in recoverable enzyme and protein.
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/bit.260220207
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  • 94
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    Studies of growth conditions in wood for three white-rot fungi and their cellulaseless mutants (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 363-376 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: White-rot fungi, which have the ability to degrade all the wood components including lignin, are of great interest in biotechnological processes based on wood and other lignocellulosic materials. It was demonstrated earlier that enough lignin can be degraded to cause a decrease in the energy demand for production of thermomechanical pulp if wood chips are pretreated by cellulaseless mutants of white-rot fungi. This paper concerns the growth conditions in wood for three white-rot fungi and their cellulaseless mutants in order to determine optimal conditions for such pretreatment processes. The pH and temperature optima have been determined as well as the growth rate in wood. The results show that the growth rate in wood. at least for Cel 44 (a cellulaseless mutant of Sporotrichum pulverulentum), is not the rate-limiting step in delignification. From different mixtures of urea and NH4H2PO4 the optimal nitrogen source was determined for the mutants. The optimal C/N ratio was found to vary between 160/1 and 400/1. It is suggested that the lower the C/N ratio, the faster the growth. It was also demonstrated that both water- and acetone-extractable substances in wood supported the growth of cellulaseless mutants. When some glucose was added to the wood, the weight loss caused by Cel 44 increased. All these observations support earlier findings that lignin in wood cannot be degraded by white-rot fungi unless a more easily metabolizable carbon source is used simultaneously.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220210
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  • 95
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    Energetic efficiency of a microbial process with an external power input: Thermodynamic approach (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 463-471 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: NO Abstract.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220217
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  • 96
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    Characteristics of hexadecane partition by the growth medium of Acinetobacter sp. (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 495-503 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The partition of n-hexadecane in the spent growth medium of Acinetobacter sp. HOI-N was determined by measuring the increase in the relative aqueous solubility of 3H-hexadecane as compared to controls. The amount of hexadecane partitioned was proportional to the protein concentration. The specific solubility of hexadecane (nmol/mg protein) was analyzed by least-squares fitting yielding an average slope of 0.6 with a standard deviation of 0.3, indicating either nonequilibrium of hexadecane or physical aggregation of protein. The amount of hexadecane partitioned was concentration dependent yielding optically clear microemulsions at hexadecane concentrations of less than 1.4mM and macroemulsions at hexadecane concentrations of 1.4mM or greater. Preliminary results indicated that hexadecane and partitioned by a lipoprotein complex.
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/bit.260220303
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  • 97
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    New device for continuously monitoring the optical density of concentrated microbial cultures (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 639-642 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220312
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  • 98
    Electronic Resource
    Electronic Resource
    Selective isolation of depressed mutants of an α-amylase yeast by the use of 2-deoxyglucose (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 651-654 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220314
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  • 99
    Electronic Resource
    Electronic Resource
    Biomass ethanol as a chemical feedstock in the United States (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980), S. 677-679 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220318
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  • 100
    Electronic Resource
    Electronic Resource
    Masthead (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 22 (1980) 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260220401
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