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Omeprazole: A Study of Its Inhibition of Gastric pH and Oral Pharmacokinetics After Morning or Evening Dosage

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      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 entericcoated 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 < 0.01) with morning dosage and 4.5 (3.0–5.6) (p < 0.01) with evening dosage. This corresponded to a >99% reduction in 24-h median hydrogen ion activity, with morning dosage having a greater effect (from 9 AM to 8 PM) (p < 0.01) than evening dosage. The relative bioavailability of omeprazole increased twofold from day 1 to day 5 of treatment with morning dosage (p < 0.02) and threefold with evening dosage (p < 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.
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