Effect of omeprazole on the anticoagulant activity and the pharmacokinetics of warfarin enantiomers in rats.
The effect of the proton pump inhibitor omeprazole on the anticoagulation and the pharmacokinetics of warfarin enantiomers was studied in rats. Omeprazole given intraperitoneally in a daily dose of 0.67 mg/kg over 8 days had no significant effect on the absorption, distribution and the total serum clearance values of the S- and R-enantiomers of warfarin. Omeprazole did not affect the pre-treatment baseline blood coagulation and the in vitro rat serum protein binding of warfarin enantiomers. In vitro study with rat liver microsomes showed that omeprazole had an inhibitory effect on the hydroxylation of warfarin enantiomers. Results obtained from in vivo urinary excretion study revealed that omeprazole inhibited the formation clearance of both S- and R-form oxidative metabolites, but increased that of the overall reductive metabolites, and the renal clearance of S- and R-enantiomers, of warfarin. As a consequence, the total serum clearance values for warfarin enantiomers remained unchanged and the hypoprothrombinaemic response produced by warfarin was not affected.
Zhou
Qingyu
Q
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Chan
Eli
E
D000465:Algorithms; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D001711:Biotransformation; D004347:Drug Interactions; D006900:Hydroxylation; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009853:Omeprazole / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014859:Warfarin / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine
D000897:Anti-Ulcer Agents; D000925:Anticoagulants; D007202:Indicators and Reagents; D014859:Warfarin; D009853:Omeprazole