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Biomedical subjects

S H Vincent

Publications and source records attributed to S H Vincent.

41 records · Page 3Linked to original sources
PubMed1977

24-hour intragastric acidity and nocturnal acid secretion in patients with duodenal ulcer during oral administration of cimetidine and atropine.

Cimetidine markedly inhibits gastric acid secretion, but from the therapeutic point of view it is important to know whether concurrent treatment with an anticholinergic increases its effect. This possibility has been investigated by measuring the 24 h intragastric acidity and nocturnal output of acid in four duodenal ulcer patients, each receiving on separate occasions cimetidine 1 g/day and placebo, atropine 2-4 mg/day and placebo, cimetidine and atropine, or two placebos. Cimetidine alone decreased mean hourly hydrogen ion activity by 63% of control values, decreased mean hourly hydrogen ion concentration (total acid) by 41%, inhibited nocturnal acid secretion by 83% and resulted in half the nocturnal samples being anacidic. Atropine alone had no effect when compared with control and combined treatment with both drugs was not superior to cimetidine alone. Atropine did not affect the absorption or urinary excretion of cimetidine. Fasting serum gastrin concentrations were not changed by any of the treatments. At the doses studied, the combination of cimetidine with an anticholinergic appears to offer no advantages over treatment with the H2-antagonist alone. Cimetidine is the only potent anti-secretory drug that does not cause acute side-effects and this important advantage would be lost if it were given with a maximal dose of an anticholinergic.

Administration, Oral↗
PubMedDate not supplied

The role of drug metabolism in drug discovery: a case study in the selection of an oxytocin receptor antagonist for development.

Drug discovery is a process involving multiple disciplines and interests. During the research phase of drug discovery, usually a large number of compounds are evaluated for biological activity and toxicological potential in animal species. Various types of problems with respect to pharmacodynamics, pharmacokinetics, and toxicity are commonly encountered at this stage. Drug metabolism, as a discipline participating in a drug discovery team, can play an important role in identifying factors underlying the problems, facilitate the optimal selection of compounds for further development, provide information on metabolites for possible improvement in drug design, and contribute to the identification of the appropriate animal species for subsequent toxicity testing. During the process of evaluating oxytocin receptor antagonists for further development for treatment of preterm labor, in vivo and in vitro drug metabolism studies conducted in rats, dogs, and monkeys contributed to the selection of L-368,899 as the development candidate on the basis of pharmacokinetic and metabolism observations. The presence of active N-demethylated metabolites of two other equipotent compounds in rats and dogs was found to be the major factor responsible for the discrepancy between oral bioavailability and efficacies observed for these 2 compounds. For L-368,899, a compound that demonstrated 20-40% oral bioavailability in rats, dogs, and chimpanzees, extensive first-pass metabolism rather than absorption was determined as the major factor responsible for the poor bioavailability (< 1%) in rhesus monkeys. In vitro metabolism studies with hepatic microsomes from rats, dogs, monkeys, and humans substantiated the conclusion that the rate of hepatic metabolism of L-368,899 in monkeys is faster than in the other species.

Animals↗