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Pharmacokinetics and pharmacodynamics of the enantiomers of warfarin in man

1974; Wiley; Volume: 15; Issue: 4 Linguagem: Inglês

10.1002/cpt1974154424

1532-6535

A Breckenridge, M. Orme, H. Wesseling, R. J. Lewis, R.P. Gibbons,

Renal function and acid-base balance

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.