Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • 1985-1989
  • 1980-1984
  • 1975-1979  (85)
  • 1979  (56)
  • 1975  (29)
  • Nuclear reactions
  • pharmacokinetics
  • 1
    Electronic Resource
    Electronic Resource
    Relationship between plasma concentration and effect of dantrolene sodium in man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 203-209 
    Details
    ISSN: 1432-1041
    Keywords: dantrolene sodium ; spasticity ; twitch tension ; dose response ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dantrolen sodium is a muscle relaxant, which is used in the treatment of spasticity. Although it is given chronically, little is known about its pharmacokinetic behaviour. The relationship between the effect of a single oral dose of dantrolene sodium and its plasma concentration in healthy volunteers was studied by measuring the effect on the twitch tension, and in spastic patients on the decrease in muscle hypertonia. On the twitch tension dantrolene gave a depression of 49.1±9.4% (±SD) within 1.15 and 3.45 h after ingestion of 100 mg. The mean maximal plasma concentration was 1.24±0.32 µg/ml (±SD). The effect and the plasma concentration were correlated. No relationship between the plasma concentration of dantrolene sodium and its effect could be established in patients, although definite activity in 6 out of 7 patients was observed after a single oral dose of 100 mg, and plasma concentration of dantrolene sodium greater than 0.3 µg/ml were consistently associated with better results than placebo treatment in 6 out of 7 patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562062
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetic model based on circulatory transport (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 287-293 
    Details
    ISSN: 1432-1041
    Keywords: linear system theory ; perfusion model ; cardiac output ; pulmonary extraction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Assessment of pharmacokinetics in terms of circulatory drug transport is proposed using the methods of linear system theory. In this model-independent approach drug distribution and disposition are characterized by the total extraction ratio, the mean residence time in the body and the volume of distribution at steady state. In analyzing concentration(c)-time(t) data, the procedure requires calculation only of the areas under the c(t)-and c(t)×t-curves to estimate kinetic parameters, and for prediction of the steady state concentration following continuous infusion or multiple doses. Pulmonary clearance of drugs is included in the theory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608408
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of bromocriptine during continuous oral treatment of Parkinson's disease (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 275-280 
    Details
    ISSN: 1432-1041
    Keywords: Parkinson's disease ; bromocriptine ; pharmacokinetics ; plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma kinetics of bromocriptine (BCT), a long-acting dopamine agonist, was studied in twelve patients with Parkinson's disease, using a newly developed gas chromatographic method of analysis. Each patient received BCT for at least three weeks in a constant but different dose regimen. Concomitant treatment with 1-DOPA was not allowed. During a 6-day hospitalization period, a blood sample was taken immediately before the afternoon dose at 14.00 h (Cmin) to determine the steady-state level. On the 6th day blood samples were collected every hour during two 8 h dose intervals. The results showed a significant correlation between the mean values of the AUC and the Cmin. First order elimination kinetics appeared to be followed by BCT, at least for the plasma concentrations commonly found. Considerable inter-individual variation was demonstrated both for the dose/plasma concentration ratio and for calculated plasma clearances. No serious side-effects were observed during the investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00618517
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Indobufen (K 3920), a new inhibitor of platelet aggregation: Effect of food on bioavailability, pharmacokinetic and pharmacodynamic study during repeated oral administration to man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 329-333 
    Details
    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; food effect on bioavailability ; repeated administration ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of food on bioavailability of indobufen tablets was investigated in 6 healthy volunteers. Subsequently, the same subjects took 100 mg b.i.d. for 7 days. Plasma levels and urinary excretion of indobufen were determined by GLC. Platelet aggregation induced by several concentrations of adrenaline was determined turbidimetrically at various times after the first and last doses. The absorption of indobufen tablets was not substantially impaired by the presence of food in the GI tract, although peak plasma levels and AUCs were slightly reduced after food. Pharmacokinetic analysis of plasma and urinary levels of indobufen did not indicate any change in drug disposition after repeated dosing. Adrenaline-induced platelet aggregation was markedly inhibited for up to 12 h after the first dose and the intensity and duration of this effect did not change after repeated administration. A twice-daily dosing appears suitable for clinical trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558436
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Clofibrate disposition in renal failure and acute and chronic liver disease (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 341-347 
    Details
    ISSN: 1432-1041
    Keywords: clofibrate ; chlorophenoxyisobutyric acid ; disposition ; hepatitis ; cirrhosis ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of clofibrate over 96 hours was observed following single oral dose in six patients with acute viral hepatitis, six patients with liver cirrhosis, seven patients with renal insufficiency, and six control subjects. No parameter of the disposition of CPIB (active form of clofibrate) was significantly altered in acute hepatitis. In liver cirrhosis, the mean plasma half-life was unchanged compared to controls (20.9 vs. 17.5 h), but plasma clearance of the non-protein bound drug was reduced (115 vs. 243 ml×min−1), plasma protein binding was reduced (92.8 vs. 97.2 percent), and the apparent volume of distribution was increased (0.20 vs. 0.141×kg−1). In renal insufficiency plasma half-life was prolonged 2 to 6-fold, depending on the degree of renal impairment. Total plasma clearance (3.4 vs. 7.1 ml×min−1) and plasma clearance of the unbound drug (81 vs. 243 ml×min−1 were reduced in patients with renal failure, the clearance of the unbound drug being inversely correlated with the serum creatinine concentration. Renal failure was also associated with decreased protein binding and an increased volume of distribution of CPIB, and with reduced urinary excretion of CPIB and its glucuronide metabolite. The dose of clofibrate should be halved in patients with cirrhosis. In renal insufficiency, the dose should be adjusted according to the individual serum creatinine level: only 10 to 15% of the usual weekly dose should be given in complete renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558438
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    The protein binding of methotrexate by the serum of normal subjects (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 363-366 
    Details
    ISSN: 1432-1041
    Keywords: methotrexate ; protein binding ; ultrafiltration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protein binding of methotrexate by serum from eight normal volunteers was assessed by continuous ultrafiltration at pH 7.4 and 37°C. Methotrexate concentrations were measured by radioimmunoassay and the data analysed by the method of Scatchard. The major binding protein was albumin which bound 87.3% of the drug in serum. Analysis of the Scatchard plots indicated two distinct groups of binding sites. Class I was found to have 0.16±0.05 (S D) binding sites with an intrinsic association constant of 71.15±35.98 (S D)×104 M−1: Class II had 2.01±0.93 (S D) binding sites and an affinity of 0.18±0.15×104 M−1. No great change in the percentage of methotrexate bound occurred until the total concentration of the drug exceeded 50 µMol 1−1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558441
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Timolol pharmacokinetics and effects on heart rate and blood pressure after acute and chronic administration (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 243-249 
    Details
    ISSN: 1432-1041
    Keywords: timolol ; beta blockade ; pharmacokinetics ; pharmcodynamics ; acute administration ; chronic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and effects of various oral doses of timolol administered either acutely or after chronic medication for 7 days were studied in healthy volunteers. After acute administration of timolol maximum plasma concentrations were attained within 1–2 h and thereafter declined exponentially with time. The mean apparent half-life of elimination from plasma was 2.5 h and was independent of dose. Area under the plasma concentration-time curve (AUC) was proportional to the orally administered dose. Plasma concentrations, apparent elimination half-life and AUC were not altered after one week of chronic administration. The effect of timolol on heart rate and blood pressure response to three sequentially increasing ‘steady state’ work loads were studied. After acute administration of timolol maximum reduction of systolic blood pressure, resting heart rate, and the different parameters of the work-heart rate (or blood pressure) relationships were produced by 5 mg timolol. Increasing the dose prolonged the duration over which these variables were reduced. The relationship between timolol plasma concentration and inhibition of different parameters of the exercise response was hyperbolic with half maximum inhibition at concentrations of about 3–4 ng/ml of timolol and maximum inhibition above 30 ng/ml. Maximum drug effects and duration of action of timolol on the different variables were similar after acute and chronic administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608402
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and pharmacodynamic interactions of diazepam with different alcoholic beverages (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 263-270 
    Details
    ISSN: 1432-1041
    Keywords: diazepam ; alcoholic beverages ; plasma level ; pharmacokinetics ; co-ordination skills ; red wine ; white wine ; whisky
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty paid healthy students ingested diazepam 10 mg 30 min after the administration of ethanol 0.8 g/kg. The alcoholic beverage used was varied in randomized double-blind experiments, which were repeated at one-month intervals. Psychomotor performance, plasma diazepam, and alcohol concentration in breath were measured 30, 60, 90 min and 2, 3, 4, 6 and 24 h after the ingestion of diazepam. Beer and white wine elevated the plasma level of diazepam and the effect lasted for up to 2 h. Whisky elevated the diazepam level for 90 min. Red wine did not affect it significantly. The alcohol-diazepam combination impaired tracking skills and oculomotor co-ordination and enhanced nystagmus, more than diazepam alone. Red wine produced a breath alcohol concentration higher than after white wine. More nystagmus was recorded after red wine and diazepam, although white wine led to a higher plasma diazepam concentration. It appears that simultaneous ingestion of alcohol and diazepam accelerates the absorption of diazepam. This pharmacokinetic alteration may not contribute much to the combined psychomotor effects of diazepam and alcohol, which were mainly due to pharmacodynamic interaction at receptor level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608405
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Analysis of the pharmacokinetics of lithium in man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 271-277 
    Details
    ISSN: 1432-1041
    Keywords: lithium ; litarex ; single dose ; multiple dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An analysis of the single and multiple dose pharmacokinetics of lithium in 7 healthy volunteers is presented. A solution of lithium chloride was administered in single dose experiments and the same solution and a sustained release preparation were employed in multiple dose experiments, which were carried out at steady state. A fixed dose of 24 mmol was used in the single dose experiments and in the subsequent multiple dose experiments in the same subjects the same dose was administered once daily for a week. Distinct two-compartment characteristics were found, with a mean disposition rate constant (β) of 0.035 h−1±0.010 SD, corresponding to a mean biological half-life of about 19.8 h. The mean half-time of the distributory α-phase was about 1.15 h. The absorption of lithium from an orally administered solution took place with a half-time of about 0.15 h in the single dose experiments. The apparent volume of distribution of the central compartment (Vc) was 0.307 1 kg−1±0.046 SD, less than half that of Vde at equilibrium. Vdβ (Vdarea) was 0.8291 kg−1±0.184 SD and mean total body clearance was 27.6 ml kg−1 h−1±4.7 SD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608406
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 10
    Electronic Resource
    Electronic Resource
    Kinetics of canrenone after single and multiple doses of spironolactone (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 255-262 
    Details
    ISSN: 1432-1041
    Keywords: spironolactone ; canrenone ; fluorimetry ; high performance liquid chromatography ; linear kinetics ; saturation kinetics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In Study I 20 normal volunteers received a single oral dose of spironolactone 100 mg. In Study II a further 20 normal volunteers were given first spironolactone 100 mg b.i.d. and subsequently spironolactone 100 mg once a day for a further 4 days. In Study III 5 normal subjects were given a single dose of spironolactone 500 mg. The concentration of canrenone in serum was determined both by fluorimetry and HPLC for 0–48 h in Study I, 120–168 h in Study II and 0–36 h in Study III. The total AUCs after the single 100 mg dose did not differ from the AUCs within the dosing interval during steady state. The half-lives of the terminal log-linear phases were almost identical (14.99±0.80 h and 15.69±0,80 h) when determined by fluorimetry, and were sligthly, but significantly (p〈0.01), longer when determined by HPLC — 20.14±1.62 and 18.71±1.04. The mean ratio of the specific AUC determined by HPLC and the fluorimetrically determined AUC was 0.3 after the single 100 mg dose. It did not differ from the corresponding value during steady state (0.34). In contrast, the ratio after the single 500 mg dose was approximately 50% higher. Fluorimetrically determined AUCs after 100 and 500 mg doses did not show dose-proportionality in contrast to the HPLC-determined AUCs. It was concluded that Canrenone contributes much less to the conventional fluorimetric determination than was previously assumed. It may not provide more than 1/10 and 1/4 of the antimineralocorticoid activity of spironolactone after single dose and multiple doses, respectively. Whereas linear kinetics apply after single and multiple 100 mg doses of spironolactone, after 500 mg saturation kinetics must be assumed with respect to metabolism. Thus, in bioavailability studies high doses of spironolactone should be avoided. For such studies the fluorimetric assay seems to be the appropriate bioanalytical method in spite of its lower specificity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608404
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 11
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of quinidine related to plasma protein binding in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 187-192 
    Details
    ISSN: 1432-1041
    Keywords: quinidine ; plasma protein binding ; pharmacokinetics ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134–0.303 (mean 0.221). Elimination rate constant (β) varied from 0.071 to 0.146 h−1 (mean 0.113), and apparent volume of distribution (Vβ) varied from 1.39–3.20 l · kg−1β (mean 2.27). Total body clearance was 2.32–6.49 ml min−1 · kg−1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both Vβ (r=0.885, p〈0.01) and total body clearance (r=0.668, p〈0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compund and its elimination rate will remain unaffected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563104
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 12
    Electronic Resource
    Electronic Resource
    Oral absorption of cimetidine and its clearance in patients with renal failure (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 153-157 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; renal failure ; elimination half life ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration curve after a single oral dose of cimetidine 200 mg was followed in 27 patients with varying degrees of chronic renal failure (creatinine clearance 1–52 ml/min) and in 46 patients with normal serum creatinine. Compared to the latter patients, the plasma concentration was higher and the elimination rate was slower in all uraemic subjects, including a group with moderate renal impairment. The preliminary recommendations of dosage for patients with a creatinine clearance below 5 ml/min, and for patients on regular haemodialysis, is cimetidine 200 mg every 12 h, 5–15 ml/min 200 mg every 12 to 8 h, 15–30 ml/min 200 mg every 8 h and 30–52 ml/min 200 mg every 6 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563098
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 13
    Electronic Resource
    Electronic Resource
    Human pharmacokinetics of nitrazepam: Effect of age and diseases (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 163-170 
    Details
    ISSN: 1432-1041
    Keywords: nitrazepam ; epilepsy ; age ; disease ; plasma concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nitrazepam were measured by gas-liquid chromatography in: young healthy volunteers, in geriatric and psychiatric patients and in epileptic children. The disposition of nitrazepam was described in terms of a two-compartment open model. After a single oral dose of nitrazepam 5 mg the most prominent differences between the experimental groups were in the β-phase half-life-mean 29 h in the young volunteers and 40 h in geriatric patients, and in the apparent volume of distribution during the β-phase of 2.4 vs 4.8 l/kg. Total plasma clearance and the average steady state concentration in both groups were equal. The plasma level rose at a rate proportional to the β-phase half-life, and so, they were achieved more rapidly in the young than in the old subjects (3.5 vs 7.5 d). No change in steady-state level or in the half-life of nitrazepam were found during long term treatment, which indicates lack of enzyme induction or inhibition. In 95% of the epileptic children with a good to fair clinical response, the plasma concentration of nitrazepam was 40–180 ng/ml (mean 114 ng/ml). As all of the patients were on combined antiepileptic therapy, no attempt was made to correlate plasma level with therapeutic response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563100
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 14
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of clorazepate in pregnant and non-pregnant women (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 175-180 
    Details
    ISSN: 1432-1041
    Keywords: clorazepate ; nordiazepam ; pregnancy ; pharmacokinetics ; intramuscular injection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of clorazepate 20 mg was injected i.m. in 7 pregnant and 7 non-pregnant women. Blood samples were collected for one week, and urine was collected for 24 h after the dose. The concentrations of clorazepate and its metabolite nordiazepam were determined by electron capture gas liquid chromatography. There was no difference between the two groups on physical examinations. Clorazepate was rapidly absorbed and the peak concentration was reached within 2h. Mean pharmacokinetic parameters for clorazepate were absorption half life 0.77h in pregnant women and 0.56h in non-pregnant women; elimination half life 1.3h in pregnant women and 2.0h in non-pregnant women; volume of distribution: 0.43 l · kg−1 in the pregnant women and 0.33 l · kg−1 in non-pregnant women. Nordiazepam reached its peak concentration within 12h after dosing; its mean half life of elimination was 180h in pregnant women and 60h in non-pregnant women. Within 24h, 1.3% of the clorazepate was recovered in urine from pregnant women and 7% in urine from the non-pregnant women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563102
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 15
    Electronic Resource
    Electronic Resource
    Blood level of cimetidine in relation to age (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 257-261 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; H2-receptor antagonist ; aging ; single dose ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The blood level versus time curve for unchanged cimetidine after a 200 mg oral dose has been determined in 20 apparently healthy subjects, ranging from 22 to 84 years of age. A significant relationship between the area under the curve (AUC) and age was found (r=0.81; P〈0.001). The peak concentrations of cimetidine were significantly inversely related to body weight (r=−0.71; P〈0.001). The age-related increase in bioavailability of oral cimetidine, as measured by AUC, was probably due to decreased total clearance of the drug, which resulted from the opposed changes (by themselves not significant) of distribution volume towards a decrease and of half-life towards an increase with age. Reduction in the standard oral dose of cimetidine by one third to one half should be feasible in the elderly without loss of efficacy, and it may be advisable in order to obviate extreme individual responses that may occur in this population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00618514
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 16
    Electronic Resource
    Electronic Resource
    Absolute bioavailability of chlorthalidone in man: A cross-over study after intravenous and oral administration (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 35-50 
    Details
    ISSN: 1432-1041
    Keywords: chlorthalidone ; pharmacokinetics ; oral and i.v. doses ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven normal human volunteers each received a constant-rate infusion of chlorthalidone for 2 h, and the same (commonly 50 mg) single oral dose on separate occasions. The concentration of unchanged chlorthalidone was analyzed over a 100 to 220 h period in plasma, red blood cells, urine and faeces after both dosage forms. A three compartment model was required to describe the intravenous plasma concentrations in five of the subjects. A two compartment model sufficed to account for the decay of the oral plasma concentrations in all seven subjects. The mean plasma t1/2 after i.v. dosing was 36.5 h (±10.5 SD), and the mean plasma t1/2 after oral doses was 44.1 h (±9.6 SD). The mean red blood cell concentration t1/2 after i.v. doses was 46.4 h (±9.9 SD), and the mean red blood cell t1/2 after the oral doses was 52.7 h (±9.0 SD). The shorter i.v. half-live was not equally manifest in all subjects, being mainly apparent in three of them. In all cases the urinary excretion rate plots were parallel to the plasma concentration curves. As the faster decay after i.v. administration was not accompanied by increased renal clearance, the difference must have been due to non-renal mechanism. The mean total of 65.4 (±8.6 SD) % of the intravenous dose was excreted in urine over infinite time, whereas the mean total excretion after the oral dose was 43.8 (±8.5 SD) %. Faecal excretion ranged from 1.3–8.5% of dose in the i.v. study to 17.5–31.2% of dose in the oral study. The sum of the amounts present in urine plus faeces pointed strongly to an important metabolic route of elimination of chlorthalidone. Bioavailability estimates (F) from three sets of data were — a mean F of 0.61 from plasma concentrations, 0.67 from urinary excretion measurements and 0.72 from the erythrocyte concentrations. Simulations with a non-linear model indicated lesser validity of the estimate from erythrocyte concentrations. It was concluded that the average of plasma and urine data, F=0.64, yielded the best estimate of the oral availability of chlorthalidone 50 mg in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563556
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 17
    Electronic Resource
    Electronic Resource
    Disposition of guanethidine during chronic oral therapy (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 121-125 
    Details
    ISSN: 1432-1041
    Keywords: guanethidine ; chronic therapy ; urinary excretion ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma level and urinary excretion rate of guanethidine have been measured in 30 patients during oral maintenance therapy, and in 5 patients following discontinuation of therapy. A significant correlation was found between the daily average urinary excretion and the maintenance dose, although wide interindividual variation was noted among patients maintained on the same dose. A statistically significant correlation was also observed between the area under the plasma level curve during the dose interval and the oral maintenance dose. After discontinuation of chronic therapy, the half-life of 1.5 days of the initial phase of elimination was essentially in agreement with the half-life of almost 2 days determined in acute studies. In addition, a second phase of elimination with a half-life of 4 to 8 days was observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609875
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 18
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of the placental transfer and distribution of clorazepate and its metabolite nordiazepam in the feto-placental unit and in the neonate (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 181-185 
    Details
    ISSN: 1432-1041
    Keywords: clorazepate ; nordiazepam ; pregnancy ; placental transfer ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clorazepate 20mg was given i. m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. “Total nordiazepam”, i.e. the sum of clorazepate and its metabolite nordiazepam, was determined by gas-liquid chromatography in maternal blood, umbilical cord blood (both arterial and venous), amniotic fluid and in milk. Clorazepate was found to cross the placental barrier slowly, but nordiazepam was transferred more rapidly. Nordiazepam was found in the milk and in the blood of neonates after breast-feeding had started.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563103
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 19
    Electronic Resource
    Electronic Resource
    Disposition pharmacokinetics of bezafibrate in man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 31-38 
    Details
    ISSN: 1432-1041
    Keywords: bezafibrate ; hyperlipoproteinemia ; bioavailability ; pharmacokinetics ; GC-MS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition kinetics of bezafibrate, a newly developed drug of great lipid-lowering potency, were investigated in normal male subjects. Five male volunteers received14C-labelled bezafibrate orally in solution, and a further 10 were given the same dose (300 mg) of un-labelled drug as tablets. The concentration of bezafibrate in serum and urine from the latter was determined by GC, and in the former total radioactivity in serum, urine and feces was followed for 48 h, and urinary excretion products were analysed by TLC and GC-MS. Rapid absorption from the gastrointestinal tract led to peak serum levels 30 min and 2 h after administration of solution and tablets, respectively. Since approximately 95% of the administered14C-bezafibrate was excreted in urine within 48 h, and almost all the remainder was detected in feces, absorption can be regarded as complete after administration in solution. The relative optimal bioavailability from the tablets was also complete, since in both cases approximately 50% of the administered dose was detected as unchanged bezafibrate in urine within 24 h by GC in the tablet study, and by TLC in the solution study. Of the decomposition products, more than 20% of the dose was present as glucuronides and the remainder consisted of several more polar compounds, one of which was identified as a hydroxyderivative of bezafibrate. Since the apparent halflife of bezafibrate in serum was 2.1 h, this new drug possesses favourable pharmacokinetic features: rapid and complete absorption, even from tablets, combined with a conveniently short half-life, and clearance which is half renal (56 ml/min) and half metabolic (43 ml/min), giving a total clearance of 99 ml/min.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00644963
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 20
    Electronic Resource
    Electronic Resource
    Pharmacokinetic, bioavailability and pharmacodynamic study of indobufen (K 3920), an inhibitor of platelet aggregation, after a single dose in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 323-327 
    Details
    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; single dose ; bioavailability ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers received single iv and oral doses of 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid 100 mg (indobufen; K 3920), an inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were determined by GLC. Collagen-induced platelet aggregation was assessed turbidimetrically at various intervals after administration. The plasma half-life of the drug was 7–8 h and more than 70% of the administered dose was recovered within 48 h in urine, as unchanged drug and as the glucuronide of indobufen. After oral administration of tablets of two different formulations, the drug was completely absorbed, but one formulation showed faster absorption. The maximal inhibitory effect on platelet aggregation was observed 1 to 4 h after iv administration, and it had decreased by 8 h. After tablets, peak effect and the time of the peak were similar, but activity was significantly prolonged, in accordance with the higher plasma levels found at 8 h. The data suggest that the effect of indobufen on platelets is reversible, and that for this drug platelets behave as a compartment that slowly equilibrates with plasma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558435
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 21
    Electronic Resource
    Electronic Resource
    Cyclobarbital as a test substance for oxidative drug metabolism in man. Findings in neuropsychiatric patients (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 433-441 
    Details
    ISSN: 1432-1041
    Keywords: cyclobarbital ; barbiturates ; pharmacokinetics ; drug interaction ; volunteers ; patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disappearance of cyclobarbital from plasma has been followed in healthy volunteers and in neurological and psychiatric patients after oral administration of one tablet of Phanodorm®, containing cyclobarbital calcium 200 mg. Plasma levels were measured by a thin-layer chromatographic method with in situ densitometry. The average t1/2 in healthy female and male volunteers was 13.3 h, and with the assumption of complete availability a mean distribution coefficient of 0.69 l/kg−1 and a clearance of 40.4 ml/min−1 were calculated. Repeated experiments in seven volunteers revealed good reproducibility of all values. When the healthy volunteers were combined with a group of untreated epileptics, a dependence of t1/2 and of the apparent volume of distribution on age was found, while clearance did not change with increasing age (range 17–54 years). Long half-lives caused by low clearance values were observed in several individuals with moderate obesity. No consistent change in cyclobarbital kinetics followed acute exposure of volunteers to alcohol or on treatment of neurological patients with carbamazepine. Patients under treatment with perazine exhibited more or less normal kinetic values. In terms of drug interaction, cyclobarbital differs from phenazone in several respects, and so it may prove a useful additional substance for measurement of the rate of drug oxidation in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561744
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 22
    Electronic Resource
    Electronic Resource
    Lorcainide infusion in the treatment of ventricular premature beats (VPB) (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 1-6 
    Details
    ISSN: 1432-1041
    Keywords: lorcainide ; ventricular premature beats ; plasma levels ; pharmacokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma level and antiarrhythmic effect of lorcainide (R 15889) have been investigated in 15 patients with ventricular premature beats (VPB). Therapy was initiated with an intravenous dose of 1.9 mg/kg given over 10 min, followed by a constant infusion of 0.18 mg/kg/h for 24 h. In 8 patients the corresponding doses were increased to 2 mg/kg and 0.27 mg/kg/h. After the intravenous doses patients were treated orally with 100 mg tid for 6–7 days. The two dosage regimens were selected so as to achieve theoretical steady-state plasma levels (css) of 200 and 300 ng/ml, respectively. The combined intravenous treatment approached (181 ± 6.8 ng/ml and 273±28.5 ng/ml, respectively) the desired css within 2 to 4 h. During the oral administration, the minimal plasma concentrations following the lower intravenous dose (184±18 ng/ml) were significantly (p=0.0001) lower than after the higher intravenous dose (264±20.5 ng/ml). The dealkylated metabolite of lorcainide was not detectable after the intravenous doses, but it accumulated during oral treatment, when its concentration exceeded that of the parent compound. In 5 of the 7 patients receiving the lower dose VPB were effectively reduced. However, in only 4 of the 8 patients on the higher dosage schedule could a significant antiarrhythmic effect be demonstrated. In addition, side effects were observed in 6 of the subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00644958
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 23
    Electronic Resource
    Electronic Resource
    Single and chronic dose pharmacokinetic studies of sodium valproate in epileptic patients (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 23-29 
    Details
    ISSN: 1432-1041
    Keywords: valproate ; epilepsy ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In four refractory epileptic patients, peak plasma levels of sodium valproate occurred within 1.5 to 3 h after a single oral dose of valproate and the decline in plasma levels followed a monoexponential course with a t1/2 of 11.4 ± 0.1 h. The mean value for apparent volume of distribution was 0.176 ± 0.013 l/kg and for total plasma clearance 0.0106 ± 0.0009 l/h/kg. Steady state plasma levels were predicted using the method of superposition utilizing pharmacokinetic parameters determined following a single dose of valproate and were 78–123% of the predicted values for two patients receiving valproate alone, and 37–64% of the predicted values for the two patients receiving carbamazepine in addition to valproate. In a further group of 20 patients the mean daily doses of valproate for 8 patients receiving valproate alone (25.4 ± 4.9 mg/kg) was significantly less than those for the 12 patients receiving concomitant anticonvulsant therapy (41.6 ± 12.3 mg/kg) (p〈0.005). In addition, the steady state predose plasma levels of valproate were significantly higher in the valproate alone patients (90.3 ± 8.7 µg/ml) compared to the patients receiving additional anticonvulsants (75.3 ± 13.8 µg/ml) (p〈0.01). The higher dose requirements of valproate and lower predose and steady state plasma levels for those patients on multiple anticonvulsants indicate an interaction between valproate and other anticonvulsants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00644962
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 24
    Electronic Resource
    Electronic Resource
    Absolute bioavailability of quinidine in two sustained release preparations (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 45-48 
    Details
    ISSN: 1432-1041
    Keywords: quinidine ; slow release formulation ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of quinidine in two sustained release preparations A and B has been compared in three females and three males with i.v. administration of quinidine. The initial rate of oral absorption did not differ between the two drug preparations; the peak concentration was observed after 4 h both for A and B, but was significantly higher after B. A slower decrease in plasma concentration was observed after preparation A than B. Absolute bioavailability did not differ significantly between A (median value 78.4%) and B (median 87.1%). Drug absorption in vivo was in good agreement with the results of in vitro dissolution tests on both preparations. The slower decrease in plasma concentration found for the new sustained release form of quinidine should be of clinical advantage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00644965
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 25
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of cephacetrile in patients undergoing haemodialysis (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 49-52 
    Details
    ISSN: 1432-1041
    Keywords: cephacetrile ; haemodialysis ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cephacetrile were studied after its administration as a single i.v. bolus injection of 15 mg/kg body weight to 11 patients with terminal renal inpairment undergoing haemodialysis for 6 h. A two-compartment kinetic model was used to describe the biphasic decrease in plasma concentration. The quantities of antibiotic in the central and peripheral compartments, and the amounts eliminated, were calculated for different times. During haemodialysis sessions, the average pharmacokinetic parameters of cephacetrile determined at the dialyser input were: α=5.03 h−1,β=0.458 h−1, K12=2.337 h−1, K21=1.996 h−1 K13=1.154 h−1, Vc=5.508 l, Vp=6.448 l, Vdss=11.956 l. As a function of the pharmacokinetic parameters of cephacetrile, a regimen of multiple doses was established for patients with terminal renal impairment, which will guarantee safe and effective concentrations of the antibiotic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00644966
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 26
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of methadone during maintenance therapy: Pulse labeling with deuterated methadone in the steady state (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 53-57 
    Details
    ISSN: 1432-1041
    Keywords: methadone ; mass fragmentography ; pulse labeling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A technique is presented for study of steady state kinetics of methadone using pulse labeling with deuterated methadone (d3) and mass fragmentography to measure both unlabeled and labeled methadone in blood. Seven subjects maintained on methadone for at least 10 months were admitted to a closed metabolic ward. The daily dose of unlabeled methadone (d0) was substituted by one dose of methadone-d3 and plasma levels of methadone-d0 and methadone-d3 were followed for 48 h using a precise (SD±5%) and sensitive (30 pmol/ml) mass fragmentographic technique. Plasma half-lives (t1/2) for both methadone-d0 and metadone-d3 were calculated from samples obtained 8–24 h following the dose of methadone-d3. The t1/2 of oral methadone-d3 was shorter (22±2 h) than that of methadone-d0 (52±20 h). The same pattern was observed after intravenous administration. The results indicate multiple pools of methadone in the body.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00644967
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 27
    Electronic Resource
    Electronic Resource
    Prazosin, pharmacokinetics and concentration effect (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 177-181 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; alpha receptor blockade ; blood pressure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and effects of prazosin have been studied after intravenous and oral dosing (1 mg) to 6 normal male volunteers. The mean terminal (β) half-life was 2.9 h after intravenous and oral routes. Oral bioavailability was 56.9%. The effects of prazosin on blood pressure were more pronounced after intravenous than oral administration, and the hypotensive effect greater on erect blood pressure. There was a significant correlation (P〈0.02) between the fall in blood pressure and the plasma drug concentration after intravenous prazosin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562058
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 28
    Electronic Resource
    Electronic Resource
    Influence of the defective metabolism of sparteine on its pharmacokinetics (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 189-194 
    Details
    ISSN: 1432-1041
    Keywords: sparteine ; pharmacogenetic defect ; defective metabolism ; pharmacokinetics ; renal excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sparteine is metabolized by N1-oxidation, which in some subjects is defective. The defect has a pronounced effect on the kinetics of the drug. In non-metabolisers elimination of sparteine proceeds entirely via renal excretion by a capacity-limited process, 99,9% of the dose being excreted as unchanged drug. In metabolisers the drug is mainly eliminated by metabolic degradation. Pronounced differences in β-phase half-life and total plasma clearance were observed between metabolisers (156 min; 535 ml · min−1) and nonmetabolisers (409 min; 180 ml · min−1).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562060
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 29
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of metformin after intravenous and oral administration to man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 195-202 
    Details
    ISSN: 1432-1041
    Keywords: metformin ; biguanides ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of14C-metformin have been studied in five healthy subjects after oral and intravenous administration. The intravenous dose was distributed to a small central compartment of 9.9±1.61 ( $$\bar X$$ ±SE), from which its elimination could be described using three-compartment open model. The elimination half-life from plasma was 1.7±0.1 h. Urinary excretion data revealed a quantitatively minor terminal elimination phase with a half-life of 8.9±0.7 h. After the intravenous dose, metformin was completely excreted unchanged in urine with a renal clearance of 454±47 ml/min. Metformin was not bound to plasma proteins. The concentration of metformin in saliva was considerably lower than in plasma and declined more slowly. The bioavailability of metformin tablets averaged 50–60%. The rate of absorption was slower than that of elimination, which resulted in a plasma concentration profile of “flip-flop” type for oral metformin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562061
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 30
    Electronic Resource
    Electronic Resource
    Food-induced reduction in bioavailability of atenolol (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 327-330 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; food intake ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the bioavailability of the beta-adrenoceptor blocker atenolol was assessed by measurement of its single-dose kinetics in ten healthy volunteers, who took 100 mg both in the fasting state and together with a standardized breakfast. Food intake significantly shortened the time to reach peak concentration (2.7 h vs 1.5 h), but caused a significant reduction in AUC values, the mean decrease being 20%. The elimination half-life was unaffected. Atenolol, which is relatively hydrophilic, is incompletely absorbed in the fasting state, and escapes first-pass metabolism. The present findings indicate that food intake causes further impairment of its absorption, even though the absorption rate may initially be enhanced. This contrasts with previous observations on the more lipophilic beta-adrenoceptor blockers propranolol and metoprolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00605630
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 31
    Electronic Resource
    Electronic Resource
    Multicompartment pharmacokinetics of netilmicin (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 331-334 
    Details
    ISSN: 1432-1041
    Keywords: netilmicin ; radioenzymatic assay ; drug accumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single dose of netilmicin (NM) was studied in 6 healthy volunteers. Elimination of the drug was followed in serum and urine for 24 h and 72 h, respectively. NM concentrations were measured with a modified radioenzymatic assay. A three compartment open model was employed to calculate the pharmacokinetic parameters. Following the rapid initial distribution, biphasic elimination with half lives of 1.99 h (t1/2β) and 36.89 h (t1/2γ) was demonstrated. Measurable amounts of NM were excreted in the urine for up to 72 h. The volume of distribution at steady-state (Vdss) of 0.68 l/kg was 3 to 4 times larger than previously reported for this antibiotic. NM plasma clearance was 91 ml/min and the renal clearance was 67 ml/min. The data indicate that on repetitive dosing the amount of drug in the body would be considerably underestimated if the prolonged terminal elimination phase were not taken into account. During prolonged treatment, accumulation of NM in renal and other tissues is likely to occur, as has been described for other aminoglycosides. The possible consequences of this pharmacokinetic behaviour are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00605631
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 32
    Electronic Resource
    Electronic Resource
    Bioavailability and pharmacokinetics of cimetidine (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 335-340 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; enterohepatic circulation ; irregular absorption ; bioavailability ; pharmacokinetics ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of cimetidine have been studied in healthy volunteers after administration of single intravenous (100 mg) and oral doses (100, 400 and 800 mg). After i.v. administration, the kinetics of cimetidine could be described by a linear, two compartment open model. Substantial variation in half-life was observed between subjects, with a mean value of 2.1 h (range 0.9–4.7). Cimetidine had a low hepatic extraction ratio and a high total plasma clearance, due to extensive urinary excretion of unchanged drug. After oral administration, the plasma concentration vs time curves in most subjects exhibited two marked peaks, an observation that seemed to be constant within individuals and was independent of dose. Bioavailability, estimated as the area under the plasma concentration vs time curves (AUC), after oral doses as compared to the intravenous dose, in most cases exceeded 100%. There was no correlation between bioavailability estimated as AUC and as urinary excretion of unchanged drug. These observations may indicate an enterohepatic circulatory mechanism, predominantly after oral administration. Both unchanged drug and its sulphoxide metabolite appear to be excreted in bile. The latter was shown in vitro to be reduced to cimetidine by fecal bacteria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00605632
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 33
    Electronic Resource
    Electronic Resource
    Haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, and its interaction with metoprolol in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 9-13 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; metoprolol ; haemodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of the selectiveβ 1-adrenoceptor agonist prenalterol were studied in healthy subjects before and after therapeutic doses of the selectiveβ 1-adrenoceptor blocker metoprolol. Plasma levels of the drugs were also determined in order to calculate certain pharmacokinetic variables. Intravenous infusion of prenalterol 0.13, 0.25 and 0.50 mg induced a dose-dependent decrease in total electromechanical systole (QA2) and pre-ejection period (PEP). The effect on left ventricular ejection time (LVET) was not significant. Increases in systolic blood pressure and heart rate were dose-dependent. Diastolic blood pressure did not change significantly. When metoprolol had been administered in a cumulative dose of 150 mg (mean maximal plasma level, 284 nmol/1) prenalterol had to be administered in doses that were twelve times higher than before theβ-blocker in order to induce the same haemodynamic effects. Prenalterol was rapidly distributed with an average half life of 8 min. This indicates that distribution equilibrium will be achieved within 30 min after intravenous administration. The overall elimination rate in the post-distributive phase corresponded to an average half life of 2.0 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563552
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 34
    Electronic Resource
    Electronic Resource
    Influence of food on the absorption of phenytoin in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 269-274 
    Details
    ISSN: 1432-1041
    Keywords: phenytoin ; food-intake ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the absorption of phenytoin was examined in eight healthy volunteers, by study of single-dose kinetics following ingestion of phenytoin 300 mg either with a standardized breakfast or on an empty stomach. Blood samples were collected at regular intervals from 0 to 48 h, and serum concentrations of unmetabolized phenytoin were determined by gas chromatography. Serum concentrations of the major metabolite of phenytoin, 4-hydroxyphenytoin, were measured by mass fragmentography. Concurrent intake of food and phenytoin appeared to accelerate absorption of the drug from the formulation used, and the peak concentrations were significantly higher (mean increase 40%) in the postprandial than in the preprandial state. As reflected by the AUC (area under the curve), the amount of drug absorbed was increased during postprandial conditions, although the difference only reached borderline significance. It is suggested that phenytoin should always be taken in a defined relation to meals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00618516
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 35
    Electronic Resource
    Electronic Resource
    A pharmacokinetic study of neostigmine in man using gas chromatography-mass spectrometry (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 367-371 
    Details
    ISSN: 1432-1041
    Keywords: myasthenia gravis ; neostigmine ; gas chromatography-mass spectrometry ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To permit rational evaluation of the empirical pharmacotherapy of myasthenia with cholinesterase inhibitors, a sensitive and selective method for the determination of neostigmine has been developed. Analysis is based on ion-pair extraction of neostigmine into methylene chloride and determination by gas chromatography-mass spectrometry (chemical ionization). As neostigmine was found to be metabolized in plasma in vitro, deuterated (d6) neostigmine was immediately added to the plasma sample as the internal standard. The limit of quantitation of the method was about 1 ng/ml (∼ 3nmol/l). The kinetics following i. v. administration were studied in four patients, who received neostigmine 2.5–3.0 mg iv to antagonize pancurone administered during anaesthesia. Elimination was rapid with a half-life t1/2 (β-slope) of 0.89±0.05 h (mean ± SE). The volume of distribution was 1.08±0.11 l/kg and plasma clearance was 0.84±0.04 l/kg/h. In three fasting myasthenic patients plasma concentrations of neostigmine were followed for 5 h after a single oral dose of 30 mg. Considerable interindividual differences in absorption were expressed in the peak concentrations, which occurred 1–2 h following drug ingestion. The bioavailability of neostigmine was estimated to be 1–2% of the ingested dose. Neostigmine concentration in plasma was found to differ considerably (up to forty-fold) between myasthenic patients on their ordinary dose-schedules of cholinesterase inhibitors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558442
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 36
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of dihydroquinidine in congestive heart failure patients after intravenous quinidine administration (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 101-105 
    Details
    ISSN: 1432-1041
    Keywords: dihydroquinidine ; congestive heart failure ; intravenous administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of dihydroquinidine were studied in 8 patients with congestive heart failure following a 22 min intravenous infusion of a quinidine preparation that contained 5.9% dihydroquinidine as an impurity. Using a thin layer chromatography-fluorometric assay procedure for dihydroquinidine, the post-infusion plasma dihydroquinidine concentrations declined biexponentially. The half-life of the fast and slow dispositional processes was 4.42±1.81 min and 6.52±2.40 h, respectively. The central compartment volume for dihydroquinidine in these patients was 0.44±0.11 l/kg with an overall apparent volume of distribution of 1.14±0.38 l/kg. The computed values of total body plasma clearance of dihydroquinidine ranged from 1.29 to 2.69 ml/min/kg with a mean value of 1.94±0.60 ml/min/kg. In these patients, approximately 16% of the administered dihydroquinidine dose was excreted intact into the urine in 48 h. The estimated value of renal clearance was 0.314±0.129 ml/min/kg. When compared to control cardiac patients, the data showed that the apparent volume of distribution for dihydroquinidine is smaller in patients with congestive heart failure and as a result of this diminished volume, the clearance rate of dihydroquinidine was slower. The net effect of these differences was the production of higher plasma concentrations of dihydroquinidine in the heart failure group.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563115
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 37
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of cefoxitin in patients with normal or impaired renal function (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 119-124 
    Details
    ISSN: 1432-1041
    Keywords: cefoxitin ; renal impairment ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefoxitin have been determined after a single i.v. injection of 15 mg/kg body weight in 10 patients with normal renal function and 20 patients with varying degrees of renal impairment. The kinetics of the antibiotic followed an open two-compartment model. In patients with normal renal function the following pharmacokinetic parameters were found: $$\begin{gathered} \begin{array}{*{20}c} {\alpha = 8.66 h^{ - 1} } & {\beta = 1.21 h^{ - 1} } & {K_{12} = 3.47 h^{ - 1} } \\ \end{array} \hfill \\ \begin{array}{*{20}c} {K_{21} = 3.17 h^{ - 1} } & {K_{13} = 3.15 h^{ - 1} } & {V_c = 4.24 l.} \\ \end{array} \hfill \\ \begin{array}{*{20}c} {V_p = 4.87 l.} & { Vd_{ss} = 9.11 l.} \\ \end{array} \hfill \\ \end{gathered}$$ In the patients with renal impairment there was a significant decrease in $$\mathop \alpha \limits_, \mathop \beta \limits_, $$ K12, K21 and K13, and an increase in the apparent volume of distribution. The degree of plasma protein binding in patients with normal renal function was 73.6% and this was diminished in patients with renal impairment. A linear relationship between K13 of cefoxitin and creatinine clearance was demonstrated. The dosage regimen for patients with renal impairment should be adjusted by modifying the dosage interval whilst maintaining the amount administered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563118
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 38
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of theophylline in young children with asthma: Comparison of rectal enema and suppositories (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 133-139 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; pharmacokinetics ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six children, aged 2 months – 4 years, received theophylline 5–6 mg/kg intravenously. Its disposition could be described by a two-compartment open model, the mean serum half life (t1/2 β) was 3.75 h, i. e., shorter than in adults, but there was a considerable interindividual variation (1.8–7.0 h, in one patient 13.3 h). Thirteen children (2 months – 4 years) received theophylline suppositories in a dose of 3.8–5.0 mg/kg, and ten (6 months – 4 years) in a dose of 8.4–14.5 mg/kg. Absorption was slow (mean half-time 43 min), incomplete and variable (biological availability 8–100%, mean 80%). Only four of the patients given the higher dose and none given the lower dose reached a therapeutic serum concentration (10–20 µg/ml). Nine children (6 months – 4 years) received rectal enemas of theophylline 4.1–9.2 mg/kg. Absorbtion was rapid (mean half-time 5.5 min) and biological availability averaged 100%. Six patients reached a serum concentration within the therapeutic range. Using the mean values of the calculated pharmacokinetic parameters, rectal enemas providing a dose of theophylline of 6–8 mg/kg t. i. d. were computed to give serum concentrations between 8–20 µg/ml, without producing too high a level during the absorption phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563120
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 39
    Electronic Resource
    Electronic Resource
    Kinetics of salicylates in blood and joint fluid (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 279-285 
    Details
    ISSN: 1432-1041
    Keywords: salicylate ; synovitis ; osteoarthritis ; arthritis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Samples of blood and joint fluid from 30 patients who had taken buffered acetylsalicylic acid were examined for concentrations of total salicylates (TSA), acetylsalicylate (ASA) and salicylate (SA). The data were arranged in groups according to diagnosis of the joint disease. Analysis of the data did not show significant difference in the kinetics of TSA into blood. In groups the time to first appearance of 0.3 mg/l averaged 6.3 min for TSA; these values averaged 7.7 min for ASA and 10.9 min for SA. Close to maximum concentrations in blood averaged 18.9 mg/l for TSA, 3.3 mg/l for ASA, and 23.3 mg/l for SA. The time for first appearance of 0.3 mg/l of total salicylates in joint fluid ranged from 10 to 34 min with an average of 18.1 min; the values of ASA averaged 19.4 min and those of SA 21.9 min. The maximum concentration in joint fluid averaged 15.7 mg/l for TSA, 2.5 mg/l for ASA, and 14.5 mg/l for SA. Transport of salicylates from blood to joint fluid showed a pattern consistent with the type of joint disease. Support was found for the hypothesis that diffusion was the major factor in the movement of salicylates from blood to joint fluid.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608407
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 40
    Electronic Resource
    Electronic Resource
    The disposition of intravenous doxapram in man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 411-416 
    Details
    ISSN: 1432-1041
    Keywords: doxapram ; intravenous infusion regimen ; pharmacokinetics ; data-point weighting ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of intravenous doxapram in healthy individuals is consistent with a three-compartment open model. Doxapram was administered by bolus injection (1.5 mg · kg−1) and by intravenous infusion (6.5 mg · kg−1 for 2 h) to 5 subjects on separate occasions. There was no significant difference in mean terminal plasma half-lives (355 and 448 min) or in mean total body clearances (5.9 and 5.6 ml · min−1 · kg−1) following i. v. bolus injection or infusion respectively. In 3 subjects plasma doxapram concentrations during and after i. v. infusion agreed with those predicted from pharmacokinetic values obtained from the bolus injection study. Since mean steady-state concentrations (9.9 µg · ml−1) would be reached only after an extended interval (mean 15.2 h), a variable-rate infusion regimen was calculated to produce and maintain a concentration of 2 µg · ml−1 from 15–25 min onwards. A regimen in which the infusion rate is reduced step-wise is recommended to achieve early near-constant plasma doxapram concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568202
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 41
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of a single oral dose of muzolimine in cardiac failure (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 105-108 
    Details
    ISSN: 1432-1041
    Keywords: muzolimine ; cardiac failure ; pharmacokinetics ; high ceiling diuretics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a new “high ceiling” diuretic, muzolimine (Bay g 2821), were investigated after a single oral dose of 40 mg in 7 patients with cardiac failure (Stages I–IV, New York Heart Association classification), and in 2 healthy subjects. Plasma concentrations peaked 1–3 h after administration and declined according to a two-compartment model. The α-phase (distribution phase) lasted until 12–16 h after administration and the mean t1/2α was 3.6 h (range 2.3–4.7) in patients, and 2.6 h (range 2.3–2.9) in healthy subjects. The mean t1/2β was 13.5 h (range 7.4–22.4) in the patients and 14.0 h (range 12.4–14.6) in healthy subjects. T1/2β was not correlated with the degree of heart failure or with the area beneath the plasma concentration curve, which varied three-fold. The renal clearance of muzolimine was in the range 2.7–15.3 ml · min−1 in 5 subjects in whom it was investigated. The pharmacokinetics of muzolimine appear not to be significantly altered by cardiac failure. The prolonged half-lives of the drug are probably responsible for the longer duration of diuretic action reported for muzolimine than for furosemide and bumetamide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609872
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 42
    Electronic Resource
    Electronic Resource
    Absorption of digoxin in severe right heart failure (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 115-120 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; right heart failure ; absorption ; absolute bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of digoxin has been investigated in 8 patients before and after successful treatment of severe right heart failure.3H-digoxin 0.1 mg as a solution, and un-labelled digoxin 0.25 mg as a tablet, were given to fasted patients. Blood samples were taken at various time intervals up to 120 hours and urine was collected over the same period. The concentrations of labelled digoxin in plasma and urine were measured in a liquid scintillation counter, unlabelled digoxin was estimated by radioimmunoassay, and various pharmacokinetic parameters were calculated. There was no significant difference in the plasma concentration curves in severe right heart failure and after its successful treatment, nor did any of the calculated pharmacokinetic parameters change significantly. Therefore, inhibition of the absorption of digoxin appears unlikely. In an additional study to estimate absolute bioavailability two different groups of patients in severe right heart failure were given3H-digoxin 0.1 mg or unlabelled digoxin 0.25 mg i. v. and the pharmacokinetic parameters were compared with those from the previous study. The bioavailability of the3H-digoxin solution and of the digoxin tablet were in the same range as values previously published for healthy volunteers, and patients both with and without cardiac failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609874
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 43
    Electronic Resource
    Electronic Resource
    Plasma levels and negative chronotropic effect of metoprolol following single doses of a conventional and sustained-release formulation (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 97-103 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; tachycardia ; healthy subjects ; conventional tablets ; slow release tablets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and associated reduction in exercise-induced tachycardia have been examined following the administration of single doses of metoprolol in conventional and slow-release tablets at different times to six healthy male subjects. The study was carried out in two parts. Initially, the tablets were given at 9 a. m. and the subjects were studied up to 14 h and then at 24 h. Subsequently, the same doses were given at 9 p. m. and the subjects were studied 12–24 h after drug administration (i. e. 9 a. m.–9 p. m. the next day). After giving the slow-release tablets the peak plasma levels were significantly lower but the drug persisted in the plasma at higher levels than after the conventional tablet. However, the beta-blocking effect was comparable from the two dosages. The results obtained for the period 12–24 h after the evening dose differed from the corresponding values after morning administration in that the plasma levels were higher and the betablocking effects more marked. Furthermore, the half-life values calculated from these data were significantly longer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609871
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 44
    Electronic Resource
    Electronic Resource
    Plasma and urinary levels of triamterene and certain metabolites after oral administration to man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 39-44 
    Details
    ISSN: 1432-1041
    Keywords: triamterene ; pharmacokinetics ; diuretic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma and urinary levels of triamterene and two metabolites were measured using a specific method of analysis. Urinary excretion was completed after 48 h, which permitted a rough estimate of its half-life as longer than two hours. The areas under the curve were 672.5±160.3 and 1.311.3±399.1 µg/ml × h after the triameterene 150 mg and 300 mg p.o., respectively and correspondingly 4.2±1.4% and 3.7±0.6% of the dose were excreted as unchanged drug. The principal metabolite of triamterene found was the sulfate conjugate. The area under the curve of this metabolite amounted to 6.672±2.120 and 11.941±5.005 µg/ml × h after the of 150 mg and 300 mg triamterene doses, respectively. The urinary excretion of the metabolite varied between 25.0±4.0% and 17.5±3.5% of the dose after either dose. In healthy subjects an effect on sodium excretion was observed after a dose of 150 mg, whereas the potassium-retaining effect was observed only after the dose of 300 mg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00644964
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 45
    Electronic Resource
    Electronic Resource
    Single- and multiple-dose kinetics of oral lorazepam in humans: The predictability of accumulation (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 159-179 
    Details
    ISSN: 1573-8744
    Keywords: lorazepam ; benzodiazepines ; pharmacokinetics ; drug accumulation ; antipyrine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Six healthy volunteers participated in single- and multiple-dose pharmacokinetic studies of oral lorazepam. Following single 4-mg oral doses, peak plasma lorazepam concentrations ranging from 40 to 70 ng/ml were reached within 3 hr of the dose. Values of absorption half-life averaged 25min (range 10.3–42.7min), and elimination half-life (t 1/2β ) averaged 14.2 hr (range 8.4–23.9 hr). During 15 consecutive days of 3 mg per day administered in divided doses, accumulation to the steady-state condition was complete within several days of the initiation of therapy. Values of accumulation half-life (mean 21.1 hr) were slightly longer than t 1/2β , and the two were not well correlated. Observed accumulation ratios (mean 1.88) were very close to those predicted from the single-dose study (mean 1.77), but the correlation between the two (r=0.51) was not significant in the small sample size. “Washout” half-life values (mean 14.9 hr) were highly correlated with t 1/2β (r=0.92). Clearance of a single intravenous dose of antipyrine determined prior to the multiple- dose lorazepam study (mean 0.86 ml/min/kg) was essentially identical to that determined after the study (mean 0.87 ml/min/kg). Overall, the rate and extent of lorazepam accumulation during multiple dosage were reasonably well predicted by the single-dose kinetic study. However, accurate prediction for any specific individual was not always achieved. Stimulation or inhibition by lorazepam of its own clearance probably does not explain imprecise prediction, since single-dose t 1/2β .
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059736
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 46
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics of procainamide infusions in relation to acetylator phenotype (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 69-85 
    Details
    ISSN: 1573-8744
    Keywords: procainamide ; pharmacokinetics ; constant-rate infusion ; acetylator phenotype ; pharmacogenetics ; renal impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of procainamide was determined in 21 lidocaine-resistant patients who received the drug according to a pharmacokinetically designed double-infusion technique. Thirteen patients were phenotyped as slow acetylators, seven as fast, and one as intermediate. The total body clearances (ClT) of PA in slow and fast acetylators were 22.6 and 34.8 liters/hr, respectively. The fraction of PA cleared by the formation of NAPA in the corresponding acetylator group was 0.2 and 0.4. Renal impairment affected the pharmacokinetics of PA more profoundly as the ClTs of PA in patients with and without renal impairment were 17.9 and 31.2 liters/hr, respectively. None of the calculated volumes of distribution was affected by acetylator phenotype or renal impairment. These data identify the contribution of at least two of the major factors accounting for variability in PA disposition in patients undergoing therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059442
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 47
    Electronic Resource
    Electronic Resource
    Disposition of synthetic glucocorticoids I. Pharmacokinetics of dexamethasone in healthy adults (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 249-264 
    Details
    ISSN: 1573-8744
    Keywords: dexamethasone ; pharmacokinetics ; renal excretion ; high-performance liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of dexamethasone alcohol is described in six male and six female healthy adult volunteers who each received 8 mg of dexamethasone phosphate by bolus intravenous injection. Quantitation of the alcohol was done using a high-performance liquid Chromatographic method with improved specificity. Statistical evaluation of the results generated by nonlinear least-squares regression analysis of the plasma concentration-time data shows that the phosphate ester is very rapidly hydrolyzed to the alcohol and a biexponential equation is the simplest poly exponential equation that is consistent with the data. The terminal phase half-lifet 1/2β was significantly greater (p〈0.05) in males (mean 201.5 min) than in females (mean 142.3 min). The prolongedt 1/2β in males did not appear to be caused by an impaired capacity to eliminate dexamethasone since the total plasma clearance did not differ between males (mean 247.5ml/min) and females (mean 242.9 ml/min). There was, however, a high positive correlation betweent 1/2β and $$V_{d_{ss} } $$ among the 12 adults (r=0.92, p〈0.001). There were also significant correlations between $$V_{d_{ss} } $$ and body weight (r=0.67, p〈0.05) andt 1/2β (r=0.80, p〈0.01).The difference in body weight between the sexes seems to be the main factor contributing to the difference observed in t 1/2β. An average of only 2.6% of the dose was found unchanged in a 24-hr urine sample, and hence it appears that dexamethasone is primarily eliminated by extrarenal, probably hepatic, mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060016
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 48
    Electronic Resource
    Electronic Resource
    Chlorpheniramine. II. Effect of the first-pass metabolism on the oral bioavailability in dogs (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 383-396 
    Details
    ISSN: 1573-8744
    Keywords: chlorpheniramine ; pharmacokinetics ; oral absorption ; first-pass effect ; saturation kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of chlorpheniramine has been studied in six dogs by following the time course of plasma concentration of the drug after intravenous and oral administration of its maleate salt in solution form. After intravenous dosing the decline in chlorpheniramine plasma concentration was typically biexponential. The drug distributed rapidly and extensively to the extravascular tissues. The mean distribution phase halflife was 12.5 min, and the mean apparent volume of distribution, Vdβ, was 525% ofthe body weight in four dogs with normal hematocrits. The mean half-life of elimination was 1.7hr. The percent absolute availability following oral administration of the drug in the aqueous solution form was found to be dose dependent. At 100-mg dose, in six dogs, an average of 36% of the orally administered dose was found to be systemically available. At 50-mg dose, in one of the four dogs studied, no measurable plasma levels of chlorpheniramine were obtained, and the average bioavailability was only 9.4%. The average availability in four dogs at 200-mg dose was 39.4%. Even at 200-mg oral dose, the dogs did not show any signs of sedation and remained alert all through the experiment. Saturable first-pass gut and/or hepatic elimination has been postulated. The possible implications of these findings on the therapeutic effectiveness of the usual dosing regimen of chlorpheniramine in dogs are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062536
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 49
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of clonidine in the rat and cat (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 481-494 
    Details
    ISSN: 1573-8744
    Keywords: clonidine ; pharmacokinetics ; blood and brain levels ; liver clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To investigate the pharmacokinetic behavior of clonidine, rats were given clonidine intravenously at 125, 250, and 500μg/kg and blood clonidine concentrations were followed for 6 hr. The disposition of clonidine in two brain regions was studied in rats after an i. v. dose of 500 μg/kg. The liver clearance in rats was investigated by liver perfusion techniques. The results obtained indicate that the disposition characteristics of clonidine can be described by a two-compartment open model in both rats and cats. The penetration of clonidine into tissues is rapid, and brain levels in rats were about 1.7 times higher than blood levels. Brain tissues were found to be an indistinguisible part of the central (blood) compartment. Dose-dependent pharmacokinetic behavior was found for clonidine in rats at the doses used. This was demonstrated by a decrease of both the rate constant of distribution to the peripheral compartment and the overall elimination rate constant from the body, with increase in dose. As a consequence, the volume of distribution and the clearance both decreased with increasing dose. Possible explanations for the dose-dependent behavior of clonidine are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062390
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 50
    Electronic Resource
    Electronic Resource
    Potential pitfalls in the conventional pharmacokinetic studies: Effects of the initial mixing of drug in blood and the pulmonary first-pass elimination (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 527-536 
    Details
    ISSN: 1573-8744
    Keywords: instantaneous distribution ; pharmacokinetics ; pulmonary first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The classical concept of assuming that an i.v. dose instantaneously distributes into the central or plasma compartment is reviewed, as is the potential for pulmonary first-pass effect. Based on available literature, the concept is shown to lead to serious errors in estimating pharmacokinetic parameters, particularly for drugs with high clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062393
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 51
    Electronic Resource
    Electronic Resource
    Multiple receptor responses: A new concept to describe the relationship between pharmacological effects and pharmacokinetics of a drug: Studies on clonidine in the rat and cat (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 495-510 
    Details
    ISSN: 1573-8744
    Keywords: clonidine ; pharmacokinetics ; analgesia ; blood pressure effects ; smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The time course of an observed pharmacological effect is affected not only by the kinetics of the drug levels at the site of action but also by parameters such as the slope and maximum effect of the functional relationship between drug level and response. Using clonidine as a test drug, it was found that the kinetics of its effects on blood pressure and pain responses cannot be described by the time course of clonidine levels in the blood, brain, or the hypothetical tissue compartment of the two-compartment characteristics of this drug. However, the results can be explained assuming that the observed pharmacological effects of a drug are composed of the sum of responses from at least two receptor sites with different slopes and maximal effects. The effect of intravenously administered clonidine on blood pressure in the rat was found to be related to the blood concentrations at least at two receptor sites with opposite effects, one leading to a hypertensive and the other to a hypotensive response. Predictions indicate that a maximum decrease of arterial blood pressure is obtained when the steady-state blood concentration of clonidine is about 1 ng/ml and that no effect is seen at 10 ng/ml. Higher levels will produce an increase of the pressure. The kinetics of the analgesic effect of clonidine in the rat could best be related to the brain levels if the observed effect was considered to be derived from the sum of activity at two receptor sites each producing analgesia. The kinetics of the effects of clonidine on the nictitating membrane of the cat was found to be determined by the kinetics of the drug in the peripheral compartment of the two-compartment open model. Consideration of multiple receptor responses is suggested for future studies on the relationship between the kinetics of drug levels and pharmacological responses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062391
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 52
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of digoxin: Relationship between response intensity and predicted compartmental drug levels in man (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 47-61 
    Details
    ISSN: 1573-8744
    Keywords: digoxin ; pharmacokinetics ; response kinetics ; three-compartment model ; serum digoxin kinetics ; systolic time intervals ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A study designed to investigate the relationship between the pharmacokinetics of digoxin and a measure of its pharmacological effect has been conducted. Serum digoxin concentrations and systolic time intervals were measured concurrently in 12 normal male volunteers following a 1.0 mg i.v. bolus injection. The averaged serum digoxin concentration- time and response-time data were analyzed pharmacokinetically using a three-compartment open model and nonlinear least- squares fitting. When only the serum level-time data were analyzed, a close relationship was found between calculated digoxin levels in the slowly distributing (deep) peripheral compartment and response of the heart to digoxin, as measured by changes in the QS2 index δQS2I. Although it was not possible to distinguish clearly a linear from a nonlinear relationship between digoxin levels in the deep compartment and δQS2I, the nonlinear relationship gave the best overall fit when both serum digoxin and δQS2I data were fitted simultaneously. The simultaneous fityielded a total body clearance of digoxin of 3.6 ml/min/kg and a terminal t1/2 of 42 hr.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059440
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 53
    Electronic Resource
    Electronic Resource
    Kinetics of biotransformation of clonazepam to its 7-amino metabolite in the monkey (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 87-95 
    Details
    ISSN: 1573-8744
    Keywords: clonazepam ; in vivo biotransformation ; 7-amino metabolite ; pharmacokinetics ; monkeys ; anticonvulsants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetic behavior of the 7-amino metabolite of clonazepam administered exogenously and formed endogenously from the parent drug was studied in a group of rhesus monkeys using constant rate intravenous infusions. Plasma levels of the 7-amino metabolite and/or clonazepam were determined with a GC-CI-MS method. The biological half-life of the 7-amino metabolite (2.2 ± 1.0 hr) was shorter than that of clonazepam (4.9 ± 0.2 hr). Total body clearance of the metabolite (0.83 ± 0.16 liters/hr/kg) was larger than that of the parent drug (0.55 ± 0.09 liters/hr/kg). The kinetics of in vivo biotransformation were described by a two- compartment model in which formation and disposition of the metabolite follow first-order processes. The fraction of a dose of clonazepam appearing in the systemic circulation as 7-amino metabolite was 0.70 ± 0.30. This value may underestimate the actual fraction formed, if the metabolite is susceptible to first- pass metabolism following in situ formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059443
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 54
    Electronic Resource
    Electronic Resource
    Attenuation of furosemide's diuretic effect by indomethacin: Pharmacokinetic evaluation (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 265-274 
    Details
    ISSN: 1573-8744
    Keywords: furosemide ; indomethacin ; prostaglandin ; pharmacokinetics ; pharma-codynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of intravenous furosemide, 40 mg, were studied in four normal males in a crossover fashion with and without indomethacin pretreatment. In each study 16 plasma and 10 urine samples were collected over 24 hr. Fluid and electrolyte urinary losses were replaced orally throughout the study. Unchanged furosemide and indomethacin were measured using HPLC; urinary sodium was measured by flame photometry. Pretreatment with indomethacin resulted in increased and prolonged furosemide plasma levels, increased area under the curve, decreased plasma clearance, decreased renal clearance, increased half-life, no change in volume of distribution, and decreased sodium excretion and urine volume. Analysis of sodium excretion rate with time shows that the inhibiting effect of indomethacin was greater during the first 2 hr than at later times.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060017
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 55
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of phenylethylacetylurea (pheneturide), an old antiepileptic drug (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 453-462 
    Details
    ISSN: 1573-8744
    Keywords: pheneturide ; antiepileptics ; pharmacokinetics ; TLC-UV densitometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of pheneturide (a decarboxylation product of phenobarbital), used to prevent psychomotor seizures for many years, was studied in normal human volunteers. To measure the drug in plasma and urine, a highly sensitive and reproducible thin-layer chromatography-reflectance spectrophotometric assay was developed. The results show that pheneturide follows first-order kinetics in the dose range studied. Its half-life after single doses is 54 hr (range 31–90), and its total body clearance (100% nonrenal) is 2.6 liters/hr (range 1.73–3.59). After repetitive administration, half-life is 40 hr (but clearance remains unchanged because of a lower volume of distribution). Because of the long half-life, repetitive administration results in a continuous steady-state level and makes this drug (kinetically) ideal for long-term use.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062387
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 56
    Electronic Resource
    Electronic Resource
    Plasma levels and β-blocking effect of α-hydroxymetoprolol—Metabolite of metoprolol—in the dog (1979)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 7 (1979), S. 471-479 
    Details
    ISSN: 1573-8744
    Keywords: metoprolol ; α-OH-metoprolol ; active metabolites ; pharmacokinetics ; β- blocking effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The plasma levels and the β- blocking effect of metoprolol and its active metabolite α- hydroxymetoprolol have been studied after i.v. bolus injections of the substances to dogs. For both substances the β- blockade increased with the dose, and there was a linear relationship between percent reduction in exercise heart rate and the logarithm of plasma concentration. The dose of the metabolite, however, had to be 5 times higher than that of metoprolol to induce the same degree of β- blockade. Because of differences in the volume of distribution, 2.0 liters/kg for α- OH-metoprolol and 3.5 liters/kg for metoprolol, the 5 times higher dose of α- OH-metoprolol resulted in 10 times higher plasma levels of the metabolite than of metoprolol. α- OH-Metoprolol was more slowly eliminated (t1/2∼7.0 hr, total body clearance ∼3.5 ml-kg−1-min−1) than metoprolol (t1/2∼2.0 hr, total body clearance ∼20.0 ml-kg−1-min−1). Approximately 5% of an i.v. dose of metoprolol was metabolized to α- OH-metoprolol. The half-life of the endogenously formed metabolite was the same as after an i.v. dose of the compound.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062389
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 57
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of di-n-propylacetate in epileptic patients (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 97-105 
    Details
    ISSN: 1432-1041
    Keywords: Di-n-propylacetate ; 2-propyl-valeric acid sodium salt ; pharmacokinetics ; anti-epileptic ; drug monitoring ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the anti-epileptic drug di-n-propylacetate (DepakineR) have been studied in 7 patients, in whom plasma concentrations were determined during and following subchronic treatment. Elimination of the drug appeared to follow a monophasic exponential course; biological half lives were 8 to 15 hours. The data supported the assumption that an open one-compartment model can be used to describe the kinetics of dipropylacetate in man. The drug appeared to have a relatively restricted distribution: calculated relative distribution volumes ranged from 0.15 to 0.40 1/kg. There were large interindividual differences in clearance rate. The therapeutic range was considered to be between 50 and 100 mg/1 plasma. Plasma levels of phenobarbital were markedly raised during treatment with dipropylacetate for an unknown reason. Determination of the plasma concentrations of drugs at accurately fixed times appears to be a reliable method for pharmacotherapeutic monitoring of epileptic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561557
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 58
    Electronic Resource
    Electronic Resource
    Concentrations of the vasodilator isosorbide dinitrate and its metabolites in the blood of human subjects (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 157-160 
    Details
    ISSN: 1432-1041
    Keywords: Isosorbide dinitrate ; pharmacokinetics ; metabolism ; pharmacological action ; nitrates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An oral dose of 5 mg of14C-isosorbide dinitrate was rapidly absorbed, biotransformed and excreted by human subjects. Peak whole blood concentrations of radioactivity were reached after 1.5 to 2 hours and declined relatively slowly. The radioactivity in whole blood mainly represented metabolites, isosorbide mononitrates. The peak concentrations found were 4.5, 11.7 and 34.3 ng/ml of isosorbide dinitrate, isosorbide 2-mononitrate and isosorbide 5-mononitrate, respectively, in the blood of one subject and 5.9, 15 and 61.3 ng/ml, respectively, in the blood of another subject. However, concentrations of the metabolites declined relatively slowly during 6 h after the oral dose. Up to 99% of an oral dose of isosorbide dinitrate was excreted during 5 days, mainly in the urine of the first day (ca. 78%). The results showed that isosorbide mononitrates were available to contribute to the pharmacological action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567108
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 59
    Electronic Resource
    Electronic Resource
    Pharmacokinetics — Uses and abuses (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 241-248 
    Details
    ISSN: 1432-1041
    Keywords: pharmacokinetics ; experimental design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It is apparent from studying recent articles on pharmacokinetics that a number of misunder-standings exist, both about the design of experiments and the analysis of results. The purpose of this paper is to outline many of the common pitfalls associated with the design of experiments and also the limitations upon the analysis of results. The paper describes mathematical, laboratory and clinical aspects which must be examined in designing a protocol for pharmacokinetic experiments. Simulated data is presented to demonstrate the dangers of using standard computer programs for parameter estimation. Even when convergence is obtained the answers may be dependent on the method employed. A mathematical model is of little use unless a reasonable amount of good, accurate data is obtained.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567122
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 60
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and side-effects of clonazepam and its 7- amino-metabolite in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 249-254 
    Details
    ISSN: 1432-1041
    Keywords: Clonazepam ; 7-amino-clonazepam ; pharmacokinetics ; side-effects ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567123
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 61
    Electronic Resource
    Electronic Resource
    Anticoagulant effect and plasma kinetics of fluorophenindione after a single dose in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 271-275 
    Details
    ISSN: 1432-1041
    Keywords: Fluorophenindione ; vitamin K antagonist ; pharmacokinetics ; loading dose ; anticoagulant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After administration of a single loading dose (80 mg p.o.) of fluorophenindione, the prothrombin level decreased to 37 % in 24 h, and the effect lasted for 48 h. Accordingly, fluorophenindione can be classified as an anticoagulant with an “intermediate” effect. Its elimination half-life was 31 h, which is longer than that of phenindione, because of the greater stability of the fluorinated derivate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567127
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 62
    Electronic Resource
    Electronic Resource
    Kinetics of nortriptyline in man according to a two compartment model (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 343-347 
    Details
    ISSN: 1432-1041
    Keywords: Nortriptyline ; pharmacokinetics ; man ; two compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nortriptyline have been assayed in four subjects after intravenous infusion of 57 mg nortriptyline hydrochloride. The data were evaluated according to a two compartment open model. The calculated best-fitting curves were in good agreement with the experimental data, better than could be expected from a simpler model. This justifies the assumption that the kinetics of nortriptyline in man may be described by this model with an appropriate input function. The data permitted estimation of all the parameters of the model. The meaning of the parameters is discussed, particularly in relation to individual variation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562660
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 63
    Electronic Resource
    Electronic Resource
    Disposition of placentally transferred carbamazepine (Tegretol®) in the newborn (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 283-284 
    Details
    ISSN: 1432-1041
    Keywords: Newborn infants ; carbamazepine ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma elimination of carbamazepine (Tegretol®) was studied in five newborns who had got the drug transplacentally from their epileptic mothers. The half-lives ranged from 8.2 – 27.7 hours which is comparable or even shorter than those found in adults after a single oral dose, but in the same range as those found in adults after multiple oral doses. This suggests that the newborns' drug metabolizing capacity has been induced during fetal life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567129
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 64
    Electronic Resource
    Electronic Resource
    The serum level approach to individualization of drug dosage (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 1-8 
    Details
    ISSN: 1432-1041
    Keywords: Serum concentrations ; individual drug dosage ; pharmacokinetics ; individual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The importance of individualizing the dosage of potent drugs in order to maximize their therapeutic effectiveness and safety is generally accepted. Whenever possible the dosage of a drug should be “titrated” directly in each patient against the intensity of its therapeutic or toxic actions. Unfortunately, for many drugs convenient clinical yardsticks of the intensity of their pharmacologic effects are lacking. Determination of the serum concentration of such compounds can help to guide adjustment of dosage during their therapeutic use. By measuring the serum level of drugs one bypasses the largest source of individual differences in doseeffect relationships — the pharmacokinetic variation between subjects. However, the relationship between the serum concentration of a drug and the intensity of its pharmacodynamic action is influenced by many other factors, which must always be considered in interpretation of serum levels. Therapeutic decisions should never be based solely on the serum concentration of a compound, nor can such measurements ever substitute for careful medical observation and judgement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613423
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 65
    Electronic Resource
    Electronic Resource
    On the fate of furosemide in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 57-61 
    Details
    ISSN: 1432-1041
    Keywords: Furosemide ; gastrointestinal absorption ; diuretics ; glucuronides ; pharmacokinetics ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 35S-furosemide was administered orally (n=7) or i.v. (n=2) to healthy subjects. The average gastrointestinal uptake estimated by comparison of the urinary recovery of label and the areas under the plasma curves after the two routes of administration was 65%. The half life of radioactivity in the plasma after oral35S-furosemide was 90 ± 17 min (estimated on the slope between 2 and 6 h); the corresponding figure after35S-furosemide i.v. was 47–53 min (slope 0.5–4 h). There was probably a slower phase after 4–6 h. Fractionation of labelled material in urine from two subjects demonstrated that approximately two thirds of the label recovered at 24 h had the same chromatographic properties as furosemide. A major part of the metabolite(s) was probably furosemide glucuronide. There was no evidence that 4-chloro-5-sulfamoylanthranilic acid was formed in man. The total urinary recovery of label (5–7 d) after oral and intravenous administration was 55.1±3.2 (mean±SD) and 82–84%, respectively. After35S-furosemide i.v., 6–9% of the label was recovered in faeces, and it could not be accounted for solely by biliary excretion of furosemide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613429
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 66
    Electronic Resource
    Electronic Resource
    Serum concentrations of ampicillin and probenecid and ampicillin excretion after repeated oral administration of a pivampicillin-probenecid salt (MK-356) (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 125-129 
    Details
    ISSN: 1432-1041
    Keywords: Pivampicillin ; ampicillin ; probenecid ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty male volunteers received oral doses (2100, 1050, and 525 mg) of a pivampicillin-probenecid salt in a 1 to 1 molar ratio (MK-356) at 12 hour intervals. After each dose peak serum concentrations of probenecid were observed 2 hours later than peak concentrations of ampicillin. Following the first dose of MK-356 the apparent elimination rate of ampicillin was dose-dependent and did not follow first order kinetics, as it showed a longer apparent half life after a higher dose. An equal dose of MK-356 administered 12 hours later caused an increase in the peak serum ampicillin level greater than expected from the concentration of ampicillin after the preceding dose. In twelve male volunteers who received at random 525 mg of MK-356 or 350 mg of pivampicillin, each three times daily for 4 days, the areas under the ampicillin concentration curve were the same after the first or last dose of either drug. When 2100 or 1050 mg of MK-356 was taken as an initial dose, 30 to 40 per cent of the ampicillin was recovered from urine in the ensuing 12 hours. The results indicate that when at least 400 mg probenecid was coadministered twice daily with 700 mg pivampicillin (MK-356), the peak serum concentrations of ampicillin were increased and its elimination rate slowed following successive doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614008
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 67
    Electronic Resource
    Electronic Resource
    Biotransformation and pharmacokinetics of sulfinpyrazone (Anturan®) in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 135-145 
    Details
    ISSN: 1432-1041
    Keywords: Anturan® ; 14C-label ; man ; pharmacokinetics ; biotransformation ; C-glucuronidation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, biotransformation and elimination of sulfinpyrazone, 1,2-diphenyl-3,5-dioxo-4-(2′-phenylsufinylethyl)-pyrazolidine, have been studied by administration of single 200 mg oral doses of a14C-labelled preparation to two male volunteers. Absorption from the gastro-intestinal tract was rapid and complete and the plasma concentration of unchanged drug reached maximum values of 22.67 and 13.04 µg/ml, respectively, after 1 – 2 hours. The elimination half-life in the two subjects, calculated from the decline between 3 and 8 hours, was 2.7 and 2.2 hours. The integrated concentration of unchanged sulfinpyrazone in plasma, estimated from the area under the concentration curves (AUC), was almost as high as that of total14C-substances, so the proportion of metabolized drug in plasma was low. In no case did the AUC of the three specifically determined metabolites, i.e. the sulphone G 31 442, the “para-hydroxy”-compound G 32 642 and the “4-hydroxy”-compound GP 52 097, exceed 4% of the sulfinpyrazone value. More than 95% of whole blood radioactivity was confined to plasma. The oral dose was rapidly and completely excreted, since within 4 days more than 95% was recovered, 85% from urine and 10% from faeces. A large proportion of the dose was excreted as unchanged drug in the two volunteers: 51 and 54% of total urinary radioactivity was present as sulfinpyrazone; 8.2 and 8.8% was present as “para-hydroxy”-metabolite, 2.7 and 3.0% as sulphone-metabolite, and 0.6 and 0.8% as “4-hydroxy”-metabolite. About 30% of urinary radioactivity consisted of highly polar metabolites. Spectroscopy of them showed that they were the C-β-glucuronides of sulfinpyrazone (28%) and the corresponding sulfone (2%). In these metabolites the C(4) of the pyrazolidine ring was directly attached to glucuronic acid, and thus they represent a new type of biosynthetic conjugate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614010
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 68
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral and intravenous doses and by repeated oral administration (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 155-159 
    Details
    ISSN: 1432-1041
    Keywords: Anticonvulsants ; benzazepines ; clonazepam ; pharmacokinetics ; gas chromatography ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy volunteers were given single i.v. and oral doses of clonazepam (2 mg). The disposition curves after i.v. administration showed a biexponential decline and the data were applied to a two-compartment open model. The volume of distribution ((Vd)β) ranged between 1.5 and 4.4 l/kg and the plasma half-life (t1/2) between 19 and 60 hours. Absorption after oral administration was fast, with peak plasma concentrations within 4 hours in all subjects. Five of the subjects received repeated oral doses of clonazepam 0.5 mg bid for 15 days. The plasma level during steady state (estimated as Cmin within the dose interval) could be predicted from the constants A, B, α and β obtained in the single dose study with a coefficient of variation of 6%. The plasma half-lives after cessation of the subchronic dosing were of the same magnitude as after single doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614012
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 69
    Electronic Resource
    Electronic Resource
    The physiological disposition of etilefrine in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 179-187 
    Details
    ISSN: 1432-1041
    Keywords: Etilefrine ; pharmacokinetics ; metabolism ; first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and metabolic studies with3H-etilefrine were performed to assess the importance of a first-pass effect on the pharmacodynamic action of this sympathomimetic amine. Identical amounts of3H-activity, ca. 80% of the dose, were excreted in the urine after intravenous or oral administration, which indicates complete enteral absorption of the drug. Comparison of the areas under the plasma curves of unchanged etilefrine after both routes of administration resulted in a bioavailability factor of 0.55, which can be explained by an extensive first-pass effect. The time curve of plasma levels of etilefrine was compatible with an open 2-compartment model characterized by a rather large volume of distribution (Vd, β) of 160 1, and a predominant half life of 2 hours. The pharmacodynamic action corresponded to the amount of drug in the central compartment. The major pathway of metabolism of etilefrine was conjugation to form the phenolic sulphate, and a very minor proportion of the drug was excreted as the corresponding hydroxymandelic acid. This metabolic pattern seems to confirm our hypothesis that phenylalkylamines with the hydroxyl group in the m-position of the benzene ring are predominantly conjugated in contrast to p-hydroxylated compounds which are mainly deaminated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614015
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 70
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium after oral administration to man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 169-178 
    Details
    ISSN: 1432-1041
    Keywords: Heptabarbital ; heptabarbital sodium ; pharmacokinetics ; plasma concentration ; single and multiple dose kinetics ; relative bioavailability ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method has been developed for the quantitative determination of heptabarbital [5-(1-cyclohepten-1-yl)-5-ethylbarbituric acid] in human plasma after administration of single therapeutic doses of the drug. It involves a single extraction step followed by gas chromatography with alkali flame ionization detection, and the results were linear in the concentration range 0.125 – 5.0 µg/ml plasma. The pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium were studied in a crossover design in 7 healthy volunteers after oral administration of 20 tablets containing 200 mg heptabarbital and hard gelatine capsules containing an equivalent amount of its sodium salt. Heptabarbital concentrations in plasma were determined at regular intervals. The absorption of heptabarbital from the tablets was quite slow and peak level times varied from 1.5 to 4 h. The sodium salt was absorbed more rapidly and peak concentrations occurred between 1/3 and 2 h. In all cases the elimination of heptabarbital could be described by a single first-order process with an average half-life of 7.6 h (range 6.1 – 11.2 h). The half-life of the drug in each individual was about the same in the two trials. The relative bioavailability in each volunteer was estimated by comparing the areas under the plasma concentration curves. The sodium salt had an average bioavailability of 83% relative to the free acid. In some volunteers urinary excretion of unchanged heptabarbital was measured; cumulative excretion amounted to 0.16 – 0.30% of the administered dose. Four volunteers received one tablet each night for eight or ten days, but no accumulation was found. In three volunteers the half-life of the drug prior to and after these experiments did not change, whereas in the other volunteer the half-life decreased from 7.1 to 4.6 h. The possibility of enzyme induction should be considered when heptabarbital is taken regularly. It was concluded that heptabarbital was a suitable drug for the treatment of insomnia, since its half-life was rather short. Heptabarbital sodium may be used for induction of sleep, whereas Medomin® tablets, i.e. heptabarbital free acid, may be prescribed when the maintenance of sleep is the primary reason for treatment with a hypnotic drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614014
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 71
    Electronic Resource
    Electronic Resource
    Interaction of indomethacin and acetylsalicylic acid as shown by the serum concentrations of indomethacin and salicylate (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 199-207 
    Details
    ISSN: 1432-1041
    Keywords: Indomethacin ; acetylsalicylic acid ; drug interaction ; oral and rectal dosing ; serum levels ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A clinical-pharmacological study was performed to determine the effect of acetylsalicylic acid upon the serum concentration of indomethacin. 14 rheumatic patients were given indomethacin orally (25 mg × 4 for 4 days) and concurrently acetylsalicylic acid 3.7 g orally (0.9 g × 3 and 1.0 g × 1 daily), and 21 rheumatic patients were given indomethacin rectally in the morning (100 mg × 1) and concurrently acetylsalicylic acid 3.7 g orally (0.9 g × 3 and 1.0 g × 1 daily). On comparison with treatment with oral or rectal indomethacin alone, it was found that peak serum concentrations of indomethacin were significantly reduced (1% level), the times of the peaks were not shifted, and the areas beneath the serum concentration curves of indomethacin were smaller, but significantly so only if compared with rectal administration. In 12 rheumatic patients given indomethacin by rectum in the evening (100 mg × 1) and concurrently acetylsalicylic acid 3.7 g (0.9 g × 3 and 1.0 g × 1 daily), the serum level of indomethacin on the following morning (after 11 h) did not differ from that found after rectal treatment. A statistically but not biologically significant difference was observed between the mean serum half-lives of indomethacin given orally and rectally. For unknown reasons, concurrent doses of acetylsalicylic acid and indomethacin made the mean serum half-life of indomethacin longer than after its oral administration, but shorter than when the same dose of indomethacin was given rectally. There was no difference between serum levels of salicylate after oral administration of acetylsalicylic acid alone or after a concurrent oral or rectal dose of indomethacin. The results have been related to those reported previously, with respect to the interaction between indomethacin and acetylsalicylic acid, the serum levels of indomethacin after oral and rectal dosing, and the serum half-life of indomethacin based upon a one- or two-compartment model. The clinical relevance of the study is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614018
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 72
    Electronic Resource
    Electronic Resource
    Disposition of quercetin in man after single oral and intravenous doses (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 229-234 
    Details
    ISSN: 1432-1041
    Keywords: Quercetin ; flavonoids ; pharmacokinetics ; absorption ; disposition ; metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quercetin, a flavonoid, have been studied in 6 volunteers after single intravenous (100 mg) and oral (4 g) doses. The data after iv administration were analyzed according to a two compartment open model with half lives of 8.8±1.2 min for the α phase and 2.4±0.2 h for the β phase (predominant half life), respectively. Protein binding was 〉98%. The apparent volume of distribution was small at 0.34±0.03 l/kg. Of the intravenous dose 7.4±1.2% was excreted in urine as a conjugated metabolite, and 0.65±0.1% was excreted unchanged. After oral administration no measurable plasma concentrations could be detected, nor was any quercetin found in urine, either unchanged or in a metabolized form. These results exclude absorption of more than 1% of unchanged drug. Recovery in faeces after the oral dose was 53±5%, which suggests extensive degradation by microorganisms in the gut. The data obtained show that oral administration of flavonoids may be of questionable value.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614022
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 73
    Electronic Resource
    Electronic Resource
    Comparison of the pharmacokinetics of glipizide and glibenclamide in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 63-69 
    Details
    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; sulfonylurea ; glipizide ; glibenclamide ; pharmacokinetics ; excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Four subjects received 5 mg14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-lives increased steadily with time. The two sulfonylureas were extensively metabolized and were excreted in the urine as hydroxylated or conjugated metabolites. The effects of both drugs on blood glucose and immunoreactive insulin were comparable. The findings are compared with other published results.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00616416
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 74
    Electronic Resource
    Electronic Resource
    Distribution and elimination kinetics of carbamazepine in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 91-96 
    Details
    ISSN: 1432-1041
    Keywords: Carbamazepine ; pharmacokinetics ; man ; diphenylhydantoin ; phenobarbital ; plasma binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carbamazepine (2.7–3 mg/kg) was administered orally as an alcoholic solution (50% v/v) to eight healthy volunteers. Two of the subjects were also given 50 mg and 100 mg of carbamazepine in alcoholic solution and 200 mg as a tablet. Plasma concentrations, which were analysed by mass fragmentography, reached a maximum 1 – 7 hours after dosing, and then declined monoexponentially with half-lives ranging from 24 to 46 hours. The half-lives were independent of dose. The apparent distribution volume ranged from 0.79 to 1.40 l/kg. It was found that 72% of carbamazepine was bound to plasma proteins with little interindividual variation, and this was not influenced by the presence of diphenylhydantoin or phenobarbital in therapeutic concentrations. The pharmacokinetic parameters calculated from single oral doses were used to predict the steady-state plasma concentration expected after treatment with multiple doses of 200 mg three times daily. The predicted steady-state concentration was 2 – 3 times higher than that reported in patients undergoing chronic treatment with carbamazepine at this dose level, i.e. the pharmacokinetics of carbamazepine apparently change during multiple dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561556
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 75
    Electronic Resource
    Electronic Resource
    The dosage of Co-trimoxazole in childhood (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 217-222 
    Details
    ISSN: 1432-1041
    Keywords: Co-trimoxazole ; sulphamethoxazole ; trimethoprim ; pharmacokinetics ; paediatric-prescribing ; dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-trimoxazole, a mixture of one part trimethoprim (TMP) and five parts of sulphamethoxazole (SMX) in fixed ratio was given to 48 children aged between one and 48 months twice daily for up to seven days. Twenty were relatively healthy and 28 were very ill. Dosage was based on age. Plasma concentrations of both drugs were measured just before a dose was due and some three hours later. They were in the effective but not toxic range and serve to justify the simple regimen which generated them.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567118
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 76
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of 5,6-trans-25-hydroxycholecalciferol, a synthetic analogue of vitamin D3, in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 255-260 
    Details
    ISSN: 1432-1041
    Keywords: Vitamin D ; renal osteodystrophy ; 5,6-trans-25-hydroxycholecalciferol ; rickets ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Vitamin D analogues of high biological activity are probably useful in the treatment of renal osteodystrophy. The pharmacokinetics of the synthetic compound 5,6-trans-25-hydroxycholecalciferol have been studied in healthy subjects who were of normal vitamin D status. In comparison to natural 25-hydroxy-cholecalciferol, serum levels of the analogue were lower and its half-life in blood after oral or intravenous administration was considerably shorter. In normal subjects no increase of dihydroxylated metabolites in serum was observed within seven days of an intravenous dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567124
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 77
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of chlormethiazole in humans (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 353-357 
    Details
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; man ; plasma levels ; gas-liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole have been studied in six healthy volunteers following an intravenous infusion of the drug. The log. plasma concentration-time curve of chlormethiazole after cessation of the infusion was found to be curvilinear and was fitted therefore, by a bi-exponential equation computed by non-linear least squares regression analysis. Half-lives for the inital α-phase (0.54±0.05 h) and the terminal β-phase (4.05 ±0.60 h) were calculated together with other pharmacokinetic parameters of the two compartment open model. An explanation for the discrepancy between the presently reported plasma half-lives and those appearing in the literature has been presented. The pharmacokinetic treatment of the plasma concentration-time data obtained following intravenous infusion also enabled the prediction that the maximal systemic availability of an orally administered dose of chlormethiazole would be of the order of 15%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562662
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 78
    Electronic Resource
    Electronic Resource
    On the pharmacokinetics of phenacetin in man (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 261-265 
    Details
    ISSN: 1432-1041
    Keywords: Phenacetin ; pharmacokinetics ; liver-first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic characteristics of the analgesic phenacetin have been determined in six healthy adults. After rapid i.v. injection of 250 mg phenacetin, the log plasma concentrations versus time curves were evaluated according to the rules of a two-compartment open model. The elimination half-life (t 1/2) β varied from 37 to 74 minutes. The volume of distribution (Vd) β ranged from 1.0 to 2.1 1 per kg body weight. The total clearance of the drug was high and approximated the average value of hepatic blood flow in normal adults. In agreement with this finding, the bioavailability of a small oral dose of phenacetin (0.25 g) was almost nil, as the bulk of the drug was cleared during its first pass through the liver. With large oral doses (1.0 g) the first-pass effect decreased and availability increased. The results are discussed and related to current general views of the liver-first-pass phenomenon.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00567125
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 79
    Electronic Resource
    Electronic Resource
    Plasma kinetics of carbamazepine and its epoxide metabolite in man after single and multiple doses (1975)
    Springer
    European journal of clinical pharmacology 8 (1975), S. 337-341 
    Details
    ISSN: 1432-1041
    Keywords: Carbamazepine ; carbamamazepine-10,11-epoxide ; pharmacokinetics ; induction of metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carbamazepine (Tegretol®) was administered orally to four patients as a single dose, and one week later three times daily for 15–21 days. The plasma half-lives of the drug were shorter in all patients after multiple doses (20.9±5.0 hours) than after the initial single dose (35.6±15.3 hours). During multiple doses the plasma concentrations of the metabolite carbamazepine-10,11-epoxide followed those of the parent drug. The steady-state plasma concentrations expected during multiple doses were calculated from the pharmacokinetic parameters obtained in the single dose studies. The calculated levels were higher (17.2±7.2 µg/ml) than the observed maximal concentrations (8.4±1.6 µg/ml on day 4), which were obtained 3–4 days after starting the multiple doses. The levels tended to decrease further during the experimental period. The results suggest that carbamazepine induces its own metabolism in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562659
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 80
    Electronic Resource
    Electronic Resource
    Derivation of general equations for linear mammillary models when the drug is administered by different routes (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 203-218 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; general equations ; mammillary models ; route of drug administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A general disposition equation for a linear mammillary model consisting of ncompartments is derived. This equation is used to derive disposition equations for the central compartment when drug input occurs into the central compartment and when drug input occurs into a peripheral compartment. The derivation of equations that describe the entire time course of drug in a particular compartment after intravenous, intramuscular, oral, and rectal drug administration is also presented.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01067909
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 81
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of digoxin in normal subjects after intravenous bolus and infusion doses (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 181-192 
    Details
    ISSN: 1573-8744
    Keywords: digoxin ; two-compartment model ; pharmacokinetics ; urinary excretion ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Normal subjects were given 0.75 mg of intravenous digoxin as a bolus and a 1-hr infusion, Radio-immunoassayed serum concentrations obtained over 48 hr and urinary excretion rates over 6 days were simultaneously fitted to a two- compartment open model by computer nonlinear least-squares regression. Serum concentration data alone were also fitted by this program. There was good agreement in calculated parameters between the two routes of administration in five of eight subjects, but the infusion mode of administration produced less variability in the apparent pharmacokinetic constants. The β half-life values obtained from serum concentration data alone (24.2 hr) underestimated the half-lives obtained by the simultaneous fit (44.1 hr). The steady-state volume of distribution of digoxin averaged 590±164 liters (±1 sd).The renal clearance of digoxin (140±41 ml/min/1.73 m 2 )was significantly higher than creatinine clearance (101±13 ml/min/ 1.73 m 2 ),indicating tubular secretion of the drug. Digoxin body clearances were 188±44 ml/min/ 1.73 m 2 ,indicating elimination of 25% of the dose by nonrenal mechanisms. Urinary excretion data are essential for proper pharmacokinetic analysis of digoxin disposition and reveal a slower rate of elimination than that suggested by earlier studies which determined only serum concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01067907
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 82
    Electronic Resource
    Electronic Resource
    Pharmacokinetics in man of theN-acetylated metabolite of proeainamide (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 223-235 
    Details
    ISSN: 1573-8744
    Keywords: N-acetylprocainamide ; procainamide ; pharmacokinetics ; drug metabolism ; clinical pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of N-acetylprocainamide (NAPA) have been studied in three normal subjects who received 500 mg of this compound by timed intravenous injection. Plasma N APA concentrations and urine excretion were measured by quadrupole mass fragmentography, and a three- compartment pharmacokinetic model was used for data analysis. NAPA elimination half-life and total distribution volume averaged 6.0 hr and 1.38 liters/kg, respectively. Renal excretion of unchanged NAPA accounted for 81% of its elimination, and the mean renal NAPA clearance was 179 ml/min. Approximately 2% of the injected NAPA was deacetylated to procainamide. The fate was not determined of 17% of the NAPA that was estimated to have been eliminated during the 16- hr study period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01066919
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 83
    Electronic Resource
    Electronic Resource
    Gas chromatographic determination and pharmacokinetics of 4-hydroxybutyrate in dog and mouse (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 99-113 
    Details
    ISSN: 1573-8744
    Keywords: sodium 4-hydroxybutyrate ; pharmacokinetics ; general anesthetics ; capacity-limited elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A rapid and reproducible method was developed to extract 4-hydroxybutyrate from plasma as 4-butyrolactone for subsequent gas chromatographic (GLC) assay. The drug, an intravenous anesthetic and oral hypnotic in man, was infused into four dogs and the plasma concentration was determined by 14 C-isotope dilution and GLC. Pharmacokinetic parameters for distribution and elimination were calculated. A capacity-limited process appears to be involved in the elimination of 4-hydroxybutyrate in the dog. Macroautoradiography revealed the distribution pattern in normal and pregnant adult mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01066018
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 84
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of morphine in plasma and discrete areas of the rat brain (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 293-302 
    Details
    ISSN: 1573-8744
    Keywords: morphine ; pharmacokinetics ; pharmacokinetic models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract After intravenous administration of an analgesic dose of morphine into rat, the time course of morphine concentrations was followed in plasma, whole brain, and four discrete areas of the brain during 8 hr. These concentration curves indicated a three-exponential function which could be described by a mammillary system of three compartments. Maximal brain levels were obtained 15–20 min after injection, showing a fairly even distribution pattern of morphine. The plasma to whole brain ratio showed three-exponential characteristics, approaching a constant value of about 4.7–4.8 after 4 hr. By use of the SAAM-25 program, the experimental data from plasma and brain were simultaneously fitted to five separate sets of three-compartment models. Results obtained implied the uniqueness of the computed transfer constants of the three-compartment model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01082303
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 85
    Electronic Resource
    Electronic Resource
    Pharmacokinetics in the aged: A review (1975)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 3 (1975), S. 387-418 
    Details
    ISSN: 1573-8744
    Keywords: review ; pharmacokinetics ; elderly ; clinical considerations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Age-related differences in drug response have recently received increased attention in the medical literature. This report reviews those recent publications dealing with the study of pharmacokinetics in the aged population. The rate and extent of drug absorption do not appear to be altered to any appreciable degree in the elderly patient. However, drug disposition in the aged subject may be affected by a number of factors including alterations in protein binding, apparent volumes of distribution, and renal and/or extrarenal clearance of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059473
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...