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Biomedical subjects

S Schenker

Publications and source records attributed to S Schenker.

At least 145 records · Page 8Linked to original sources
PubMed1980

Cimetidine impairs elimination of chlordiazepoxide (Librium) in man.

We have studied chlordiazepoxide (Librium) disposition and elimination in eight normal subjects before and after 1 week of cimetidine therapy, 300 mg orally four times a day. Cimetidine strikingly impaired the clearance of chlordiazepoxide from plasma, and this was, at least in part, due to decreased demethylation of the drug to N-desmethylchlordiazepoxide. Since the volume of distribution of chlordiazepoxide was not altered by cimetidine, the elimination half-life of chlordiazepoxide was also significantly prolonged by cimetidine therapy.

Adult↗
PubMed1980

Cimetidine spares the glucuronidation of lorazepam and oxazepam.

Lorazepam (Ativan) disposition and elimination were studied in 8 normal subjects before and after 1 wk of cimetidine therapy, 300 mg taken orally four times a day. In 4 of these 8 normal subjects the disposition and elimination of oxazepam (Serax) were also studied before and after similar treatment with cimetidine. Cimetidine did not alter the elimination of either lorazepam or oxazepam. Since both drugs are eliminated exclusively after conjugation as glucuronide, this study demonstrates a relative sparing of this pathway of biotransformation of drugs in subjects receiving cimetidine.

Adult↗
PubMed1980

Impaired elimination of caffeine by oral contraceptive steroids.

The effect of OCS on the disposition and elimination of caffeine was examined. Caffeine (250 mg) was administered orally to 13 healthy males, nine healthy females taking no OCS, and nine healthy females on OCS. The t1/2 (beta) was significantly prolonged in women on OCS (10.7 +/- 3.0 hr vs. 6.2 +/- 1.6) (p less than 0.001) as compared to women taking no OCS. Women on OCS had a significantly lower total plasma clearance (0.79 +/- 0.21 ml/min/kg vs. 1.3 +/- 0.35) and free clearance (1.12 +/- 0.28 ml/min/kg vs. 1.97 +/- 0.57) that women not taking OCS. Volumes of distribution and plasma binding were similar in both groups of females. When women taking no OCS were compared with men, all pharmacokinetic parameters were similar except for volume of distribution, which was significantly larger in the women (p less than 0.05). We conclude that OCS impair the elimination of caffeine.

Absorption↗
PubMed1979

Transport and metabolism of thiamin in isolated rat hepatocytes.

This study examines thiamin transport in isolated rat hepatocytes and its relationship to thiamin phosphorylation. In an Na+ medium, [35S]thiamin, 3 microM, was accumulated rapidly by the cells, and a near study state intra-/extracellular distribution ratio of 3 was attained in 1 min. However, the uptake of radioactivity continued to increase with time owing principally to the accumulation of [35S]thiamin pyrophosphate (TPP). In a choline, Li+ or K+ medium, the steady state intra-/extracellular distribution ratio of [35S]thiamin was decreased to less than or equal to 1.1. Accordingly, the rate of formation of [35S]TPP also decreased. Ouabain and uncouplers of oxidative phosphorylation significantly lowered the distribution ratio of intra-/extracellular [35S]thiamin. These data indicate that thiamin transport in liver is concentrative, Na+-dependent, and dependent on biological energy. Additionally, they suggest that thiamin transport plays a significant role in governing the rate of synthesis of TPP. Neither pyrithiamin, an inhibitor of thiamin pyrophosphokinase nor o-benzoylthiamin disulfide, a permeable thiamin analog, affected the distribution ratio of intra-/extracellular [35S]thiamin, but preferentially inhibited the phosphorylation of [35S]thiamin. By contrast, amprolium primarily inhibited uptake. These data suggest that thiamin transport and phosphorylation can be differentiated by the action of appropriate inhibitors.

Animals↗
PubMed1979

Disposition of chlordiazepoxide: sex differences and effects of oral contraceptives.

There is considerable interspecies and interdrug variability in the effect of sex differences and oral contraceptive (OC) steroids on hepatic drug elimination. Their influence on the disposition of chlordiazepoxide has been studied in 11 healthy young men (29 +/- 5 yr), 11 healthy young women (28 +/- 5 yr), and 7 healthy women receiving OC steroids (27 +/- 2 yr) for more than 6 months. The elimination half-life (t1/2(beta)) was longer (from 14.8 +/- 5.9 hr to 8.9 +/- 2.5 hr) and protein binding less (95.5 +/- 1.4% and 97.0 +/- 1.2%) in women than in men. Weight-normalized plasma clearances of total drug did not differ, but the clearance of unbound drug was significantly less in women (8.7 +/- 5.0 ml/min/kg) than in men (15.6 +/- 5.3 ml/min/kg). Women on OC steroids had a lower plasma binding (from 93.6 +/- 1.5% to 95.5 +/- 1.4%) and a higher volume of distribution (from 0.62 +-/ 0.23 l/kg to 0.40 +/- 0.14 l/kg) than women not on OC steroids. The elimination t1/2 was longer (from 24.3 +/- 12 hr to 14.8 +/- 5.9 hr) and the clearance of unbound drug lower (from 5.7 +/- 3.0 ml/min/kg to 8.7 +/- 5.0 ml/min/kg) in women on OC steroids than in those not using them, but these differences were not statistically significant.

Adolescent↗
PubMed1979

Plasma binding of benzodiazepines in humans.

Plasma binding of chlordiazepoxide, diazepam, loraxepam, and oxazepam was determined by equilibrium dialysis in 20 male, healthy volunteers, 25-86 years old. A wide range of binding was observed, with the free fraction varying twofold for lorazepam, fourfold for chlordiazepoxide and diazepam, and over 20-fold for oxazepam. Statistically significant linear relationships were not observed between the degree of binding and age, serum albumin, or total protein for any of the drugs. There was, however, a correlation between the extent of binding for the four drugs. Because of the importance of unbound benzodiazepine levels in eliciting any pharmacological response and also in disposition, consideration of the wide interindividual variability in plasma binding must be made in interpreting pharmacodynamic and pharmacokinetic data.

Adult↗
PubMed1979

Drug prescribing in hepatobiliary disease.

Liver disease in man is associated with a variety of pathophysiological processes which may influence the disposition of drugs in several ways. Interpretation of the observed pharmacokinetic changes in liver disease requires an understanding of the relationship between systemic drug clearance (Cls), volume of distribution (Vd) and the elimination half-life [t1/2(beta)], i.e. t1/2(beta) = 0.693 . Vd/Cls. Half-life will be a measure of the fluctuation in drug level one may expect with continued administration of a drug while clearance will determine the dose required to achieve a particular steady state level. Liver disease may affect clearance and volume of distribution and so produce changes in half-life; in addition, alterations in plasma binding of drugs may occur and so influence free (unbound) drug levels. It is also possible that the end organ response, particularly in the case of sedative drugs, may be affected by liver disease. Other factors such as age, nutrition, smoking, and concomitant drug therapy may also influence drug elimination in patients with liver disease. At the present time, caution should be exercised in prescribing drugs to patients with liver disease and the dose should be titrated to the clinical response. The development of liver 'function' tests using model or marker drugs may offer some help to the prescriber in the future and enable a less empirical approach.

Adrenal Cortex Hormones↗
PubMed1979

Physostigmine reversal of diazepam-induced hypnosis. A study in human volunteers.

Under randomized double-blind conditions, 1.00 to 1.67 mg of intravenous physostigmine (Antilirium) reversed sleep induced by administration of 0.102 to 0.238 mg/kg body weight of intravenous diazepam in eight healthy human volunteers. Awakening occurred 330 to 740s after initiation of the physostigmine infusion at a rate of 0.5 mg/min every 4 min. Diazepam plasma levels were not significantly different at the start of either the physostigmine or placebo infusion. Physostigmine did not effect plasma binding of diazepam. Six subjects experienced nausea, and one subject developed an arrhythmia. Physostigmine reverses diazepam-induced hypnosis but causes side-effects requiring cautious administration.

Adult↗