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Pharmacokinetics and pharmacodynamics of the enantiomers of warfarin in man
Abstract
The rate of elimination, apparent volume of distribution, plasma clearance, and relative anticoagulant potency of the enantiomers of warfarin have been determined in man. In 9 subjects the plasma half‐life (T½) of R warfarin after a single oral dose of 0.5 mg/kg ranged from 19.9 to 69.S hours, and was significantly longer than that of S warfarin, which ranged from 18.0 to 34.1 hours. There was no significant difference in the apparent volume of distribution of the enantiomers, and thus the plasma clearance of R warfarin was significantly less than that of S warfarin. After multiple dosing to steady state, the plasma T% of R warfarin in 8 subjects ranged from 37.4 to 88.6 hours and was significantly longer than that of S warfarin, which ranged from 21.2 to 42.6 hours. The apparent volume of distribution of the enantiomers was the same, and thus the plasma clearance of R was again significantly less than that of S warfarin. The plasma T½ of R but not of S was significantly longer after multiple dosing than after a single dose. The ratio of the steady‐state plasma concentration of R to S warfarin was 3.80 : 1 in 4 patients with the same degree of anticoagulant control. The relative dose requirements of R to S warfarin were 1.5.9 : 1 in these sub;ects. S warfarin is a more potent anticoagulant than R warfarin in man.
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Cited by
Pharmacogenetics of Warfarin Elimination and Its Clinical Implications
Takahashi, H., & Echizen, H. (2001) · Clinical Pharmacokinetics · doi:10.2165/00003088-200140080-00003 · Cited by 312
Considerations when prescribing trimethoprim-sulfamethoxazole
Ho, J. M. W., & Juurlink, D. N. (2011) · Canadian Medical Association Journal · doi:10.1503/cmaj.111152 · Cited by 232
“Of these, the latter is roughly five times more biologically active and is metabolized by cytochrome P450 2C9.(66,67) Co-prescription of trimethoprim–sulfamethoxazole increases S-warfarin levels in most patients.”
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