Pentagastrin-stimulated gastric acid secretion and pharmacokinetics following single and repeated intravenous administration of the gastric H+, K(+)-ATPase-inhibitor pantoprazole (BY1023/SK&F96022) in healthy volunteers

Z Gastroenterol. 1990 Sep;28(9):443-7.

Abstract

The objective of the study was to investigate the pharmacodynamics and pharmacokinetics of the gastric H+, K(+)-ATPase inhibitor pantoprazole in man following repeated i.v. dosing. 8 healthy male volunteers aged from 25 to 31 years (median: 29 years), body weight between 72 and 95 kg (median: 82 kg) entered this single-blind two-period cross-over study. Each subject underwent two treatment periods of 5 days each with daily infusion of 15 mg or 30 mg pantoprazole, respectively. A placebo day preceeded the trial. On the placebo day as well as on days 1, 4 and 5 of each treatment period, gastric secretion was stimulated submaximally by a pentagastrin infusion of 0.6 micrograms/h/kg over a period of 4 h, starting one hour before administration of drug or placebo. Repeated once-daily infusion (15 min) of pantoprazole resulted in a rapidly increasing pharmacodynamic effect: as compared to placebo the mean percent inhibition of acid output measured from 1 to 3 h after start of infusion was 22%, 63% and 78% for the 15 mg dose, and 56%, 97% and 99% for the 30 mg dose on days 1, 4 and 5, respectively. The pH also increased in relation to the dose and the duration of treatment. Mean fasting gastrin serum concentrations increased by about 50%, yet remained within the normal range. Only in one subject, one of the individual values was above the upper limit of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Adult
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / pharmacokinetics
  • Benzimidazoles / pharmacology*
  • Gastric Acid / metabolism*
  • Gastrins / blood
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Omeprazole / analogs & derivatives
  • Pantoprazole
  • Pentagastrin / pharmacology
  • Single-Blind Method
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*
  • Sulfoxides / administration & dosage
  • Sulfoxides / pharmacokinetics
  • Sulfoxides / pharmacology*

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Benzimidazoles
  • Gastrins
  • Sulfoxides
  • Pantoprazole
  • Sodium-Potassium-Exchanging ATPase
  • Pentagastrin
  • Omeprazole