Omeprazole: a study of its inhibition of gastric pH and oral pharmacokinetics after morning or evening dosage.

Pharmacodynamic and pharmacokinetic studies of omeprazole, a new gastric antisecretory agent, were undertaken in 8 healthy subjects. The drug was administered orally as an encapsulated enteric-coated granulate (40 mg daily at 9 am or 9 pm for 5 days), and its effect on the integrated 24-h gastric pH was determined, together with its apparent bioavailability. The pretreatment 24-h median pH was 1.9 (interquartile range 1.4-2.9). After 5 days of treatment, the median pH had risen to 5.0 (3.7-6.0) (p less than 0.01) with morning dosage and 4.5 (3.0-5.6) (p less than 0.01) with evening dosage. This corresponded to a greater than 99% reduction in 24-h median hydrogen ion activity, with morning dosage having a greater effect (from 9 am to 8 pm) (p less than 0.01) than evening dosage. The relative bioavailability of omeprazole increased twofold from day 1 to day 5 of treatment with morning dosage (p less than 0.02) and threefold with evening dosage (p less than 0.02), suggesting that increased absorption of this acid-labile drug occurs with increasing inhibition of acid secretion. We conclude that this formulation of omeprazole presently being used in clinical trials is a highly potent antisecretory agent in humans, although its optimal effect may not be observed for several days.