THE EFFECT OF OMEPRAZOLE PRETREATMENT AND COTREATMENT ON CERIVASTATINABSORPTION AND METABOLISM IN MAN

Objective: Cerivastatin, a novel HMG-CoA reductase inhibitor, is exclu sively cleared via cytochrome P450-mediated biotransformation and subs equent biliary and renal excretion of the metabolites. The presented s tudy was performed to determine the influence of the gastric acid secr etion inhibitor omeprazole on bioavailability and pharmacokinetics of cerivastatin. Method: In a controlled, randomized, non-blind two-way c rossover study single oral doses of 0.3 mg cerivastatin were administe red in 12 healthy male subjects under fasting conditions either alone or together with 20 mg omeprazole following a 4-day pretreatment with oral 20 mg omeprazole once daily. Results: The mean AUC and C-max rati os (combination treatment versus monotherapy) including 90% confidence intervals were 1.00 (0.92 - 1.09) and 0.94 (0.80 - 1.16) for cerivast atin. Similar results were obtained for the metabolites of cerivastati n and for omeprazole. Conclusion: No metabolic inhibitory interaction was noted for either cerivastatin or its major active metabolites, nor for omeprazole, respectively. In addition, the change in gastric pH a s consequence of the inhibition of gastric acid secretion exerted by o meprazole had no influence on cerivastatin absorption.