Omeprazole Acenocoumarol

The 4-hydroxycomnarins undergo biotransformation similar to warfarin, forming hydroxylated metabolites at the 6 and 7 positions. These hydroxylated metabolites accoimt for 63 to 99% of the metabolic clearance of 4-hydroxycoumarins, including acenocoumarol. The metabolic clearances of R- and S-acenocoumarol are 6 and 66 times higher than those of R- and S-warfarin, respectively [68]. The metabolism of acenocoumarol is also stereoselective in favor of the S enantiomer. Sulphaphenazole competitively inhibits the 7-hydroxylation of R- and S-acenocoumarol and the 6-hydroxylation of S-acenocoumarol. Omeprazole acts as a partial inhibitor of 6- and 7-hydroxylation of acenocoumarol enantiomers [68]. 

Beyond those in vivo examples depicted in Table 4, there are some in vitro data suggesting stereoselective drug interactions with oral anticoagulants. For example, Hermans and Thijssen [68] investigated the potential of metabolic interactions in vitro between warfarin or acenocou-marol and cimetidine, propafenone, sulphaphenazole, or omeprazole using human liver microsomes. Sulphaphenazole competitively inhibited the 7- and in some experiments the 6-hydroxylation of S-warfarin and R- and S-acenocoumarol. Omeprazole partly inhibited the 6- and 7-hydroxylation of R-warfarin, R-acenocoumarol, and S-acenocoumarol [68]. 

Aeenoeoumarol. In a placebo-controlled study in 8 healthy subjects, omeprazole 40 mg daily for 3 days had no effect on the pharmacokinetics of R- or 5-acenocoumarol when a single 10-mg dose of aeenoeoumarol was given on day 2. In addition, omeprazole did not alter the anticoagulant effects of aeenoeoumarol. Similarly, there was no evidence of an interaction in a retrospective study of 118 patients given aeenoeoumarol with omeprazole and 299 patients taking aeenoeoumarol without omeprazole (matched for age and sex). ... 

Vreeburg EM, De Vlaam-Schluter GM, Trienekens PH, Snel P, Tyt t GNJ. Lack of effect of omeprazole on oral acenocoumarol anticoagulant therapy. ScaiuiJ Gastroenterol ( 99T)... 

Garcia B, Lacambra C, Garrote F, Garcia-Plaza I, Solis X Possible potentiation of anticoagulant effect of acenocoumarol by omeprazole. Pharm WorldSci (1 4) 1 231-2. 

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