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  • 1980-1984  (1.181)
  • 1980  (1.181)
  • General Chemistry  (890)
  • Engineering General  (233)
  • pharmacokinetics
  • Nuclear reactions
Materialart
Erscheinungszeitraum
  • 1980-1984  (1.181)
Jahr
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neural transmission 49 (1980), S. 281-285 
    ISSN: 1435-1463
    Schlagwort(e): Melatonin administration ; diurnal rhythm ; dog ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): Dichloroacetate ; pharmacokinetics ; lactate ; lactic acidosis ; alanine ; glucose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-1041
    Schlagwort(e): sodium valproate ; epileptic patients ; pharmacokinetics ; plasma concentration ; prediction ; maintenance dosage
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-1041
    Schlagwort(e): prenalterol ; beta1-adrenoceptor agonist ; metabolic effects ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    ISSN: 1432-1041
    Schlagwort(e): zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 129-133 
    ISSN: 1432-1041
    Schlagwort(e): dapsone ; salivary drug elimination ; pharmacokinetics ; acetylator phenotype
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 321-326 
    ISSN: 1432-1041
    Schlagwort(e): sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 517-520 
    ISSN: 1432-1041
    Schlagwort(e): desmethyldiazepam ; oxazepam ; cimetidine ; hepatic elimination ; pharmacokinetics ; interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 449-457 
    ISSN: 1432-1041
    Schlagwort(e): alcuronium ; single dose ; multiple dose ; plasma levels ; neuromuscular response ; pharmacokinetics ; anaesthesia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 269-273 
    ISSN: 1432-1041
    Schlagwort(e): paracetamol ; thyrotoxicosis ; hypothyroidism ; drug disposition ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 419-422 
    ISSN: 1432-1041
    Schlagwort(e): alminoprofene ; antalgic ; pharmacokinetics ; single dose ; multiple doses
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 423-428 
    ISSN: 1432-1041
    Schlagwort(e): pyridostigmine ; myasthenia gravis ; pharmacokinetics ; bioavailability ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 473-477 
    ISSN: 1432-1041
    Schlagwort(e): aminophylline ; asthma ; serum theophylline ; pharmacokinetics ; prediction of serum level
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 459-463 
    ISSN: 1432-1041
    Schlagwort(e): colestipol ; fenofibrate ; fenofibric acid ; pharmacokinetics ; interaction ; volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 51-53 
    ISSN: 1432-1041
    Schlagwort(e): pethidine ; phenobarbital ; aminoglycoside antibiotics ; pharmacokinetics ; clinical response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 55-63 
    ISSN: 1432-1041
    Schlagwort(e): diuretics ; furosemide ; caffeine ; theophylline ; neonate ; pharmacokinetics ; disposition
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 195-198 
    ISSN: 1432-1041
    Schlagwort(e): ampicillin ; age ; oral dose ; i. v. dose ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 237-244 
    ISSN: 1432-1041
    Schlagwort(e): isosorbide dinitrate ; 2-isosorbide mononitrate ; 5-isosorbide mononitrate ; digital plethysmography ; hypotension ; bradycardia ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 45-50 
    ISSN: 1432-1041
    Schlagwort(e): ketobemidone ; narcotic analgesic ; N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 87-92 
    ISSN: 1432-1041
    Schlagwort(e): beta-blocker ; metoprolol ; slow-release formulation ; multiple dosing ; blood pressure ; heart rate ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 21
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 189-196 
    ISSN: 1432-1041
    Schlagwort(e): flunitrazepam ; prolonged administration ; pharmacokinetics ; clinical observations ; sleep parameters
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 22
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 275-284 
    ISSN: 1432-1041
    Schlagwort(e): chlormethiazole ; cirrhosis of the liver ; antipyrine ; protein binding ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 263-268 
    ISSN: 1432-1041
    Schlagwort(e): naproxen ; renal insufficiency ; metabolism ; protein binding ; single dose ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 355-360 
    ISSN: 1432-1041
    Schlagwort(e): cis (Z)-flupentixol ; cis (Z)-flupentixol decanoate ; serum concentration ; biological half-life ; pharmacokinetics ; first-pass metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 25
    ISSN: 1432-1041
    Schlagwort(e): atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 26
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 339-348 
    ISSN: 1432-1041
    Schlagwort(e): acebutolol ; renal failure ; dialysis ; pharmacokinetics ; N-acetylmetabolite
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 27
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 379-384 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 391-394 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 279-283 
    ISSN: 1432-1041
    Schlagwort(e): glipizide ; diabetes ; food intake ; blood glucose ; blood insulin ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 347-350 
    ISSN: 1432-1041
    Schlagwort(e): dibekacin ; renal failure ; dialysis ; pharmacokinetics ; microbiological assay ; dosage regimen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 383-390 
    ISSN: 1432-1041
    Schlagwort(e): prenalterol ; oxprenolol ; haemodynamics ; pharmacokinetics ; inotropic effects ; side effects ; tolerance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 32
    ISSN: 1432-1041
    Schlagwort(e): ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 37-43 
    ISSN: 1432-1041
    Schlagwort(e): caffeine ; idrocilamide ; xanthine derivatives ; inhibition of metabolism ; neuropsychiatric side effects ; pharmacokinetics ; healthy man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 425-428 
    ISSN: 1432-1041
    Schlagwort(e): prazosin ; congestive heart failure ; pharmacokinetics ; oral dose ; comparison with healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 25-30 
    ISSN: 1432-1041
    Schlagwort(e): pethidine ; norpethidine ; placental transfer ; pharmacokinetics ; newborns
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 109-116 
    ISSN: 1432-1041
    Schlagwort(e): diuretics ; antihypertensive agents ; renal disease ; dispositon ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 37
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 171-174 
    ISSN: 1432-1041
    Schlagwort(e): bromocriptine ; Parkinson's disease ; plasma level ; salivary level ; protein binding ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 295-299 
    ISSN: 1432-1041
    Schlagwort(e): propylthiouraci ; propranolol ; carbimazole ; methimazole ; comparative activity ; pharmacokinetics ; bioactivation ; thyroid peroxidase inhibition
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 39
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 321-328 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; hypertension ; pharmacokinetics ; plasma renin ; blood pressure effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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).
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 505-509 
    ISSN: 1432-1041
    Schlagwort(e): cefadroxil ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 209-213 
    ISSN: 1432-1041
    Schlagwort(e): disopyramide ; bioavailability ; controlled-release tablets ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 215-221 
    ISSN: 1432-1041
    Schlagwort(e): L-dopa ; elderly ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
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  • 43
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 385-391 
    ISSN: 1432-1041
    Schlagwort(e): sulpiride ; pharmacokinetics ; serum clearance ; renal clearance ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 69-74 
    ISSN: 1432-1041
    Schlagwort(e): digoxin ; neonates ; infants ; pharmacokinetics ; dosage schedules
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 83-88 
    ISSN: 1432-1041
    Schlagwort(e): patent ductus arteriosus ; indomethacin ; premature newborns ; pharmacokinetics ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 147-150 
    ISSN: 1432-1041
    Schlagwort(e): antidepressant ; geriatric ; nortriptyline ; pharmacokinetics ; prediction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 175-183 
    ISSN: 1432-1041
    Schlagwort(e): amoxycillin ; pharmacokinetics ; bedrest ; sleep ; ambulation ; renal clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: 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.
    Materialart: Digitale Medien
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  • 48
    ISSN: 1432-2048
    Schlagwort(e): Boron ; Foliar nutrition ; Nuclear reactions ; Transport (boron) ; Trifolium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: 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.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 497-507 
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetics ; symbols ; notation ; nomenclature
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 633-648 
    ISSN: 1573-8744
    Schlagwort(e): compartmental analysis ; dynamic response ; identification ; linear systems ; modeling ; parameter estimation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 99-104 
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetics ; pharmacological effects ; two-compartment model ; tissue accumulation ; aminoglycoside antibiotics ; gentamicin ; nephrotoxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 219-228 
    ISSN: 1573-8744
    Schlagwort(e): bumetanide ; diuretics ; pharmacokinetics ; three-compartment model ; protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 363-372 
    ISSN: 1573-8744
    Schlagwort(e): bretylium ; pharmacokinetics ; healthy subjects ; antiarrhythmic ; twocompartment model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 421-438 
    ISSN: 1573-8744
    Schlagwort(e): bufuralol ; renal failure ; pharmacokinetics ; metabolites ; renal clearance ; hepatic clearance ; first-pass metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
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  • 55
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 439-461 
    ISSN: 1573-8744
    Schlagwort(e): lithium ; pharmacokinetics ; physiological parameters ; cellular transport ; three-compartment model ; circadian rhythm
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 105-110 
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetics ; maintenance dose ; dose estimation ; multiple dosing
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 257-296 
    ISSN: 1573-8744
    Schlagwort(e): chemotherapy ; pharmacokinetics ; brain tumors ; modeling ; solid tumors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
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  • 58
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1-11 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The distribution of the first-passage time is of decisive importance in lift (elevator) design. It yields the easure of performance of the system, the expected number of stops, the interval (i. e. time elapsed between two successive departures from a given floor) and many other parameters and factors determining the required number of lifts in a building. The derivation is based on the transition probability matrix of the operation policy, and consists in solving a system of linear equations.
    Zusätzliches Material: 3 Tab.
    Materialart: Digitale Medien
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  • 59
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 55-62 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: Fourier analysis of numerical accuracy has traditionally concentrated on the propagation behaviour of various methods. When systems of equations in more than one unknown are involved, analysis of propagation accuracy alone is shown to be incomplete. A distribution factor is introduced to complement the Fourier analysis in these cases, and application of the concept to two problems commonly encountered in the water resources field is demonstrated. The distribution factor is shown to provide important information which cannot be obtained from the customary analysis of propagation accuracy.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
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  • 60
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 177-188 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: A simple approximation by nonconforming finite elements is presented that passes the patch test of Irons and Strang but does not yield approximate solutions converging to the solution of the given boundary value problem. It is constructed from continuous piecewise linear functions perturbed by step functions. Further, strange convergence properties of such approximations are explained in all details because they may be typical for the behaviour of nonconforming finite elements violating the basic precondition for convergence.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
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  • 61
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 209-223 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The solution of incompressible, viscous flow problems using the primitive variable finite element approach is formulated in a coherent and physically reasoned exposition. In particular, it is shown that terms associated with changes in momentum caused by lack of mass conservation should logically be included in the governing equations. Previous formulations have not considered this possibility. Numerical results are presented to show the effect of inclusion of these extra terms; however, it is concluded from the numerical results for the specific case which was tested that there is no obvious benefit obtained by including these terms.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
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  • 62
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 237-247 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: A dual load method of truss analysis is presented that allows highly nonlinear member behaviour to be followed. In particular, a brittle type of strut behaviour is considered. The method assumes that the inelastic strut response is known and that piecewise linearization of the behaviour is acceptable. An example is given to illustrate the type of problem that can be handled. The example involves negative stiffness of the members and consequently attention must be given to the equation solving procedure for the structure. A comparison is made with some observed test results.
    Zusätzliches Material: 11 Ill.
    Materialart: Digitale Medien
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  • 63
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 291-295 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: A numerical Laplace transform inversion technique is described, which is a modification of the inversion method using an exponential series representation. By adding an auxiliary function and using Erdélyi's inversion formula, the proposed technique provides the inverse approximation with improved accuracy near t = 0. Numerical illustrations shows that this procedure also works in cases when the original method of schapery fails to give satisfactory results.
    Zusätzliches Material: 4 Tab.
    Materialart: Digitale Medien
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  • 64
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 308-318 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: A new method for interpolating in triangles is described. Bivariate cubic polynomials are utilized to define an interpolant which assumes arbitrary position and slope on the entire boundary of a triangular domain. Some examples and applications are discussed.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
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  • 65
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 351-360 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: Numerical convergence of first- and second-order plate-bending elements is investigated. Using iso-parametric formulation, general bilinear and biquadratic quadrilaterals, with the three moment components and the transverse deflection as dependent variables, are obtained. The same elements are also used as degenerate triangles by collapsing one side. A constant bending moment patch test, applied numerically to the elements, indicated poor performance for linear triangles, while the bilinear, quadratic and biquadratic elements behaved well, with exact results in uniform meshes. Further numerical examples showed the same general trend as the patch test. Although bilinear, quadratic and biquadratic elements were always able to yield the correct solutions with mesh refinements, the linear triangles were in general unable to do so.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
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  • 66
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 381-404 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The complete two-dimensional partial differential equations for developing laminar flow in a circular tube have been treated by a finite difference analysis. Property variation with temperature, especially that of viscosity, is allowed for in a flexible manner. The continuity and momentum equations, and then the energy equations, are solved by direct elimination at each axial step, and marching procedure used in the axial direction. A new technique is that the stepwise energy balance is rigidly satisfied throughout by using it as a constituent equation in place of the ‘explicit’ wall thermal boundary condition normally used.The analysis predicts the complete developing hydrodynamic and thermal fields, together with friction factors and heat transfer coefficients. It has been tested for a range of fluid velocity and thermal boundary conditions and for various fluids, including high viscosity oils, water and air.Data for constant wall heat flux have already been published. 1,2 Predictions for constant wall temperature presented here are for forced and combined convection and are compared with experimental data of Test3 and Zeldin and Schmidt4.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
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  • 67
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 464-469 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: A numerical method for solving two-point boundary value problems associated with systems of first-order nonlinear ordinary differential equations is described. It needs four function evaluations at each point and is of order h6, where h is the space chop. Results of computational experiments, which include perturbation of the initial conditions, comparing this method with other known methods are given.
    Zusätzliches Material: 1 Tab.
    Materialart: Digitale Medien
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  • 68
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 470-476 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: An algorithm is given to discretize a polygon or curved surface into triangular arrays. The method first involves the manual division of the array into quadrilaterals with specified numbers on rows and columns. The individual points are then filled in automatically and elements are automatically generated. A point of particular importance is that the number of columns or rows may be made to change. A subroutine is given to perform this task.
    Materialart: Digitale Medien
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  • 69
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 483-494 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: An approximate analysis method for calculating local and system geometric imperfection influences on the displacements, stresses and buckling load of imperfect truss structures, is developed. The structural response, as a function of the design variables, is expressed in this approximate analysis which is much faster and cheaper than the ‘accurate’ analysis. The accurate analysis for a particular design is used as a base for each approximate analysis which then gives the response information needed for other designs in the neighbourhood about the base point design. Comparison of the approximate behaviour predictions with accurate results based on the more refined analysis methods shows that the quality of the proposed approximate analysis procedure is adequate for guiding a structural design procedure. It is evident that the approximate analysis is capable of describing the nonlinear behaviour of the structure, but when nonlinearity increases, the quality of the approximate analysis tends to deteriorate.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
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  • 70
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 575-582 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The usual linear shape function for approximating axial displacement in beam finite elements used as eccentric stiffeners leads to an inconsistency which can result in large errors in the deflection of plates or composite beams. The introduction of an additional degree-of-freedom for these elements circumvents this problem.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
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  • 71
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 639-648 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: A boundary-location method is developed for finite element simulation of steady, two-dimensional flows of Newtonian liquid with free boundaries. In the method, boundary shape and position and the velocity and pressure fields are determined simultaneously. Inertial, viscous, gravitational, and surface tension effects are included in the development. The complete set of nonlinear finite element equations is solved by a modified frontal method combined with Newton-Raphson iteration to speed convergence. The finite element used to illustrate the method approximates the pressure as a piecewise constant function and the velocity and free boundaries as piecewise linear functions. Example calculations for flow from a slit show that the method can be effective.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
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  • 72
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 685-699 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The choice on an efficient direct integration procedure for linear structural dynamic equations of motion is discussed. It is suggested that as accuracy parameter the truncation error on the exponential terms contained in the modal contributions of the exact solution be assumed. This error does not always coincide with the local truncation error. These considerations were used to design an unconditionally stable one-step method whose accuracy is 0(h4). Numerical comparisons with some well-known integration schemes showed the efficiency of the proposed method.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
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  • 73
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 713-731 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: This paper presents a generalized method which generates linear, triangular, quadrilateral and pentahedral elements for the finite element method. Depending on geometrical and material variations, the region to be discretized is manually divided into blocks such as lines, triangles, quadrilaterals, pentahedrons and hexahedrons in several appropriate co-ordinate systems. However, no connectivity information of the adjacent blocks is required by the user as input. The continuity of the generated nodal co-ordinates and element configurations at the block interface are automatically maintained to describe the geometry of structures, no matter how these five types of blocks are connected. Furthermore, a mesh grading algorithm which generates reliable mesh grade distributions in the interior of the triangular and quadrilateral blocks is established corresponding to the arbitrarily defined subdivision numbers for each edge line of blocks. This algorithm is extended to the mesh grading in the interior of the hexahedral and pentahedral blocks. Element numbers are also renumbered in this scheme, in addition to node numbers, in order to increase the computational efficiency of the global matrix assembly. Additional facilities, i.e. loading data generation, boundary condition data generation and so on, are also discussed. An illustrative and a practical example are given to demonstrate the capabilities of this scheme.
    Zusätzliches Material: 15 Ill.
    Materialart: Digitale Medien
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  • 74
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 773-778 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The shape functions of serendipity rectangular elements had originally to be found by inspection. More recently an algorithm has been developed to formalize the construction of these shape functions. Here a simple expression is found for the interpolation function of the most general serendipity element. The shape functions can be derived immediately.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
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  • 75
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 955-980 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: A series of finite element algorithms for the calculation of the post-buckling behaviour of structures are proposed. The algorithms represent a finite element implementation of a variational principle for nonlinear eigenvalue problems. Incremental amplitude solution schemes are defined. Numerical results are presented for the post-buckling behaviour of specific structures with linear and nonlinear pre-buckling states.
    Zusätzliches Material: 24 Ill.
    Materialart: Digitale Medien
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  • 76
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1041-1052 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 77
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980) 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 78
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 935-942 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 79
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 991-1020 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: This paper presents isoparametric formulation for the three-dimensional transition finite elements. The transition finite elements are necessary for applications requiring the use of three-dimensional isoparametric solid elements and the curved shell elements. These elements provide proper connections between the two portions of the structure modelled with three-dimensional solids and the curved shell elements. The element properties are derived and presented in detail. Numerical examples are also presented to demonstrate the accuracy and the applications of such elements in three-dimensional stress analysis.
    Zusätzliches Material: 14 Ill.
    Materialart: Digitale Medien
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  • 80
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1261-1278 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: A hybrid-stress element is developed for the analysis of thin and moderately thick plates. The independent transverse displacement and rotations are interpolated by the 12-node cubic Serendipity shape functions. All components of stress are included and 36β stress assumption is used. The element stiffness possesses correct rank and numerical results indicate that the element does not lock in the thin-plate limit. Results obtained using the present element are compared with those obtained using a 12-node assumed-displacement based Mindlin plate element with reduced integration; the present hybrid-stress element is shown to yield superior accuracy for all cases considered. In addition, the accuracy of the present element is compared against that of analogous 4-node and 8-node hybrid-stress Mindlin plate elements.
    Zusätzliches Material: 10 Ill.
    Materialart: Digitale Medien
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  • 81
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1280-1280 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 82
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1083-1094 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: This paper is concerned with the solution of the three-dimensional potential problem for electromagnetic river gauging. It extends previous ideas of joining finite elements in an interior region to one infinite external element treated by the boundary integral method1,2 to this case where there are two external infinite elements representing the river and the ground. The boundary continuity conditions on the infinite river-ground interface, as well as the internal-external interfaces, are dealt with by introducing a variational principle with relaxed continuity requirement3.
    Zusätzliches Material: 8 Ill.
    Materialart: Digitale Medien
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  • 83
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1107-1107 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 84
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1129-1148 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Zusätzliches Material: 20 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 85
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1113-1127 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: Various boundary methods are considered for the numerical solution of the linear wave equation. The solution in the interior region is obtained using the Lax-Wendroff method. The theory of Gustafsson, Kreiss and Sundström is used to establish stability and the theory of Sköllermo is used to compare the accuracies of the various methods. The accuracy predictions are compared with computed results.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
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  • 86
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1161-1175 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The technique of fixed-interface modal synthesis used to solve large structural eigenvalue problems is extended to fluid-structure eigenvalue problems with a view to efficient solution of problems involving localized modifications. Three cases are considered: namely, those fluid or fluid-structure vibration problems directly analogous to the structural case; the modification of the fluid model of a structure enclosing a compressible fluid; and the modification of fluid and structural models of a structure enclosing an incompressible fluid. Examples of the three cases are given, as are estimates of the computation that can be saved when using the methods to avoid resolving modified eigenvalue problems. It is also shown that the hard-walled modes of a fluid enclosure can be used to modify the incompressible-fluid modes of the fluid-structure system to account for a degree of compressibility in the fluid. An example and computation estimates are given.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
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  • 87
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1239-1260 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The assumed-stress hybrid finite element model is examined for application to the bending analysis of thin plates. A hybrid-stress functional is defined by using a Mindlin-type displacement assumption and including all components of stress. The Euler equations and matrix formulation corresponding to this functional are examined to assess the effects of plate thickness, and a rationale is presented for the selection of stress assumptions so that locking is avoided in the thin plate limit. To illustrate these concepts, a series of linear displacement quadrilateral elements are derived and tested, and the best of these elements is identified for suggested implementation in general-purpose computer programs.
    Zusätzliches Material: 11 Ill.
    Materialart: Digitale Medien
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  • 88
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1315-1324 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: An algorithm is presented for reducing the frontwidth of finite element meshes. The technique takes an arbitrary input scheme and reorders the elements so as to reduce the frontwidth. A number of examples are presented to demonstrate the reliability and effectiveness of the method.
    Zusätzliches Material: 10 Ill.
    Materialart: Digitale Medien
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  • 89
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1335-1341 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: This review attempts to place in perspective the wide variety of computer methods which are available for constructing irregular computational grids. Several different approaches exist for each aspect of the construction task: creation of the points, recognition of neighbouring points that define grid elements, enumeration of the points with indices, optimization of the positions of the points for computational advantage, and variation of point density throughout the grid.
    Materialart: Digitale Medien
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  • 90
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1381-1393 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The finite element method is used to analyse heat and mass transfer problems in porous media, in which the thermophysical properties are allowed to vary as functions of temperature and moisture. An example is given of the application of the method to the problem of timber drying.
    Zusätzliches Material: 6 Ill.
    Materialart: Digitale Medien
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  • 91
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1570-1574 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: A method is presented for solving field problems using a finite element formulation, to be executed with the aid of a micro-computer. In order to reduce the requirements regarding memory space, the coefficients of the matrix defining the system of equations are not stored, but calculated when they are needed, in a modification of the usual finite element procedure. The method is applicable to all problems for which Gauss-Seidel iteration converges, and can handle problems involving more than 100 degrees-of-freedom on a computer with 8,000 bytes memory. Computing time may run up to several minutes per cycle of iteration, but on a small, personal computer, this is still acceptable.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
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  • 92
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1659-1680 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: A finite element formulation for the adhesive of a lap joint is presented. The element is based on the assumptions common to the theories of Goland and Reissner and Ojalvo and Eidinoff. Deficiencies of the lap joint theories of those workers and of a previous finite element formulation of the adhesive are pointed out and the covergence of the new formulation to their results is discussed. Experimentally determined extreme fibre strains in the adherends are compared with those determined numerically using the new finite element formulation.
    Zusätzliches Material: 21 Ill.
    Materialart: Digitale Medien
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  • 93
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980) 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 94
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1730-1733 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 95
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1747-1769 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: Finite elements with polynomial interpolation functions of a degree higher than 2 are used comparatively little on large FEM systems, except in shell elements. However, the author has had several years' experience in the use of the so-called ‘isoparametric, reduced Hermitian element’,4 Which has behaved excellently in an industrial as well as an educational environment. The reason for the interest in the Hermitian concept is that the overcompatibility of the element reduces the number of unknowns, the solution time and the discontinuities in stresses between elements.Explicit formulae for the family of interpolation polynomials of order q and degree p = 2q + 1 are given and hierarchical Hermite elements are introduced. The families of Hermite and serendipity elements are isomorphic and the latter may thus be extended to arbitrary high order.For some problems the equidistant node configuration in Lagrange elements of degree 3 and higher is not optimal with respect to smoothness, and a new type of element, the ‘Lobatto element’, is introduced.The methods consistently produce results of an accuracy which is above the requirements of usual engineering applications, but in graphics smoothness of curves is important for a convincing representation. The methods are of particular interest in industries working with structures composed of almost linear materials with well-known properties.
    Zusätzliches Material: 10 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 96
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1771-1812 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: An assessment of flat triangular plate bending elements with displacement degrees-of-freedom at the three corner nodes only is presented, with the purpose of identifying the most effective for thin plate analysis. Based on a review of currently available elements, specific attention is given to the theoretical and numerical evaluation of three triangular 9 degrees-of-freedom elements; namely, a discrete Kirchhoff theory (DKT) element, a hybrid stress model (HSM) element and a selective reduced integration (SRI) element. New and efficient formulations of these elements are discussed in detail and the results of several example analyses are given. It is concluded that the most efficient and reliable three-node plate bending elements are the DKT and HSM elements.
    Zusätzliches Material: 21 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 97
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1613-1626 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The method of infinite elements is briefly reviewed. New more logical and general formulations of infinite elements are presented. The simplicity of the programming is emphasized. Results are given for elasticity and potential problems. Future extensions are discussed.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
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  • 98
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1681-1689 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: Convection-diffusion equations are difficult to solve when the convection term dominates because most solution methods give solutions which oscillate in space. Previous criteria based on the one-dimensional convection-diffusion equation have shown that finite difference and Galerkin (linear or quadratic basis functions) will not give oscillatory solutions provided the Peclet number times the mesh size (Pe Δx) is below a critical value. These criteria are based on the solution at the nodes, and ensure that the nodal values are monotone. Similar criteria are developed here for other methods: quadratic Galerkin with upwind weighting, cubic Galerkin, orthogonal collocation on finite elements with quadratic, cubic or quartic polynomials using Lagrangian interpolation, cubic or quartic polynominals using Hermite interpolation, and the method of moments. The nodal values do not oscillate for collocation or moments methods with Hermite cubic polynomials regardless of the value of Pe Δx.A new criterion is developed for all methods based on the monotonicity of the solutions throughout the domain. This criterion is more restrictive than one based only on the nodal values. All methods that are second order (Δx2) or better in truncation error give oscillatory solutions (based on the entire domain) unless Pe Δx is below a critical value. This value ranges from 2 for finite difference methods to 4·6 for Hermite, quartic, collocation methods.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 99
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 16 (1980), S. 149-170 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Notizen: The purpose of the paper is two-fold: Firstly, we develop stream function--vorticity and primitive variable finite element models of two-dimensional barotropic equations that satisfy the conservation of mean vorticity, mean squared vorticity (or enstrophy) and mean kinetic energy, and scondly, we present a comparative study of a number of numerical schemes for their accuracy in phase speed as well as in amplitude calculations for a two-dimensional, time-dependent, stream function--vorticity equation for periodic fluid motion in a channel. A circular vortex is placed in a uniform channel flow of a constant velocity (U) as an initial condition. An analytic solution exists for the problem such that the vortex moves with a constant speed U conserving the shape of the vortex: \documentclass{article}\pagestyle{empty}\begin{document}$$ \begin{array}{*{20}c} {\psi \left({x,y,0} \right) = - Uy + \psi _0 \exp \left[{ - a^2 \left({x^2 + y^2 } \right)} \right] \equiv F\left({x,y} \right)} \hfill \\ {\psi \left({x,y,t} \right) = F\left({x - Ut,y} \right)} \hfill \\ \end{array} $$\end{document} where U, ψ0 a are constants. This example makes it easier to identify the cause of phase speed error, either due to linear or non-linear processes, and furthermore, to find a satisfactory scheme for time integration. The numerical schemes compared include: Arakawa Jacobian,1 Arakawa-Matsuno scheme, Galerkin finite element, Lax-Wendroff, leap-frog, and Crank-Nicholson. The effect of a variational adjustment (see Sasaki16) is also studied. Computational time, RMS errors in stream function and vorticity, and the conservation of the mean kinetic energy and enstrophy are compared at the end of 120 (one period) and 240 (two periods) time steps. The study indicates that the numerical scheme that employs finite elements in space (same as Arakawa Jacobian) and Crank-Nicholson in time is the most accurate among the schemes studied.
    Zusätzliches Material: 24 Ill.
    Materialart: Digitale Medien
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  • 100
    Digitale Medien
    Digitale Medien
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 15 (1980), S. 1281-1282 
    ISSN: 0029-5981
    Schlagwort(e): Engineering ; Engineering General
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Mathematik , Technik allgemein
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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