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.
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)
Simon
B
B
Krankenhaus Schwetzingen.
Müller
P
P
Hartmann
M
M
Bliesath
H
H
Lühmann
R
R
Huber
R
R
Bohnenkamp
W
W
Wurst
W
W
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D010418:Pentagastrin / Q000494:pharmacology; D016037:Single-Blind Method; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013454:Sulfoxides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D005755:Gastrins; D013454:Sulfoxides; D000077402:Pantoprazole; D000254:Sodium-Potassium-Exchanging ATPase; D010418:Pentagastrin; D009853:Omeprazole