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A single, oral, 1.5-mg dose of trimoprostil was taken before a standard meal and a matching placebo was taken after a standard meal by 10 subjects (group A). A second group of 10 subjects took placebo before a meal and trimoprostil after the meal (group B), while a third group took placebo both before and after the standard meal (group C). Food-stimulated gastric acid production was measured by intragastric titration for 6.5 hr after dosing. Trimoprostil taken after the meal had a greater effect on gastric acid secretion than when taken before the meal: Duration of effect was 5 to 5.5 hr in group B and 2 to 2.5 hr in group A. Blood samples were drawn and assayed for trimoprostil by gas chromatography-mass spectrometry. Mean trimoprostil plasma concentration and mean inhibition of gastric acid secretion data were fit to two models by the Hill equation. The mean plasma concentration associated with 50% inhibition of gastric acid secretion was 1.25 ng/ml. Trimoprostil plasma concentrations between 3 and 4 ng/ml were associated with 70% to 80% gastric acid inhibition. Overall, there appears to be a pharmacokinetic-pharmacologic correlation between trimoprostil plasma concentrations and inhibition of gastric acid secretion. Trimoprostil (1.5 mg) in the presence of food appears to have a therapeutic advantage, in that it decreases acid secretion longer than when taken without food and suffers no loss of bioavailability.
R J Wills, and
R A Levine, and
B H Min, and
E H Schwartzel, and
S V Givens, and
W A Colburn, and
H E Gallo-Torres, and
M L Scheinbaum
January 1986,
Journal of clinical pharmacology,
R J Wills, and
R A Levine, and
B H Min, and
E H Schwartzel, and
S V Givens, and
W A Colburn, and
H E Gallo-Torres, and
M L Scheinbaum
January 1986,
Current medical research and opinion,
R J Wills, and
R A Levine, and
B H Min, and
E H Schwartzel, and
S V Givens, and
W A Colburn, and
H E Gallo-Torres, and
M L Scheinbaum
March 1976,
Gut,
R J Wills, and
R A Levine, and
B H Min, and
E H Schwartzel, and
S V Givens, and
W A Colburn, and
H E Gallo-Torres, and
M L Scheinbaum
March 1990,
European journal of pharmacology,
R J Wills, and
R A Levine, and
B H Min, and
E H Schwartzel, and
S V Givens, and
W A Colburn, and
H E Gallo-Torres, and
M L Scheinbaum
June 1988,
Arzneimittel-Forschung,
R J Wills, and
R A Levine, and
B H Min, and
E H Schwartzel, and
S V Givens, and
W A Colburn, and
H E Gallo-Torres, and
M L Scheinbaum
June 1981,
Clinical pharmacology and therapeutics,
R J Wills, and
R A Levine, and
B H Min, and
E H Schwartzel, and
S V Givens, and
W A Colburn, and
H E Gallo-Torres, and
M L Scheinbaum
August 1982,
British journal of clinical pharmacology,
R J Wills, and
R A Levine, and
B H Min, and
E H Schwartzel, and
S V Givens, and
W A Colburn, and
H E Gallo-Torres, and
M L Scheinbaum
December 1986,
Japanese journal of pharmacology,
R J Wills, and
R A Levine, and
B H Min, and
E H Schwartzel, and
S V Givens, and
W A Colburn, and
H E Gallo-Torres, and
M L Scheinbaum
November 1980,
Acta physiologica Scandinavica,
R J Wills, and
R A Levine, and
B H Min, and
E H Schwartzel, and
S V Givens, and
W A Colburn, and
H E Gallo-Torres, and
M L Scheinbaum
January 1983,
Renal physiology,
