The effect of omeprazole pre- and cotreatment on cerivastatin absorption and metabolism in man.
OBJECTIVE
Cerivastatin, a novel HMG-CoA reductase inhibitor, is exclusively cleared via cytochrome P450-mediated biotransformation and subsequent biliary and renal excretion of the metabolites. The presented study was performed to determine the influence of the gastric acid secretion inhibitor omeprazole on bioavailability and pharmacokinetics of cerivastatin.


METHODS
In a controlled, randomized, non-blind two-way crossover study single oral doses of 0.3 mg cerivastatin were administered 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 Cmax ratios (combination treatment versus monotherapy) including 90% confidence intervals were 1.00 (0.92 - 1.09) and 0.94 (0.80 - 1.16) for cerivastatin. Similar results were obtained for the metabolites of cerivastatin and for omeprazole.


CONCLUSIONS
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 as consequence of the inhibition of gastric acid secretion exerted by omeprazole had no influence on cerivastatin absorption.
Sachse
R
R
Institute of Clinical Pharmacology, Bayer AG, Wuppertal/Köln, Germany.
Ochmann
K
K
Rohde
G
G
Mück
W
W
D000328:Adult; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000493:pharmacokinetics / Q000494:pharmacology*; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D011725:Pyridines; C086276:cerivastatin; D009853:Omeprazole