Pharmacokinetics and pharmacodynamics of the enantiomers of warfarin in man

  title={Pharmacokinetics and pharmacodynamics of the enantiomers of warfarin in man},
  author={Alasdair M. Breckenridge and M. L. E. Orme and Harry Wesseling and Robin J. Lewis and R T Gibbons},
  journal={Clinical Pharmacology \& Therapeutics},
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… 

Disposition of warfarin enantiomers and metabolites in patients during multiple dosing with rac-warfarin.

There was a significant correlation between the estimated formation clearance of (S)-7-hydroxywarfarin and the clearance of(S)- warfarin, which accounted for much of the variability in the latter, and for the first time a stereoselective assay was employed.

Enantiomers of warfarin and vitamin K1 metabolism.

Following the administration of vitamin K1, the maximum plasma concentration and area under the plasma concentration time curve values for the metabolite Vitamin K1 2,3-epoxide were greater after S warfarin than after R Warfarin, reflecting the greater anticoagulant potency of SWarfarin.

Stereoselective interaction between the R enantiomer of warfarin and cimetidine.

The stereoselectivity of the pharmacokinetic interaction between warfarin and cimetidine was investigated in eight healthy volunteers and resulted in elevation of vitamin K1 2,3-epoxide concentrations, which were similar in each case.

Pharmacokinetics of warfarin enantiomers: A search for intrasubject correlations

The Maintenance dose of racemic warfarin required by an individual patient may be a useful predictor of the maintenance dose of S(−)‐warfarin which will produce a comparable degree of anticoagulation, and no such predictability is evident with respect to R(+)‐warFarin.

The Effects of Acetaminophen on Pharmacokinetics and Pharmacodynamics of Warfarin

The urinary excretion pattern of acetaminophen and its metabolites was not significantly altered over its course of administration, and the (R)‐ and (S)‐enantiomers of warfarin exhibited significantly different pharmacokinetic properties.

The effect of cimetidine on the steady-state pharmacokinetics and pharmacodynamics of warfarin in humans

Cimetidine stereoselectively affects the steady-state pharmacokinetics of warfarin by inhibiting the disposition of the less potent R-warfarin in humans, however, this interaction is likely to be of minimal clinical significance in most patients.

Effect of Ubidecarenone on Warfarin Anticoagulation and Pharmacokinetics of Warfarin Enantiomers in Rats

  • S. ZhouE. Chan
  • Medicine, Biology
    Drug metabolism and drug interactions
  • 2001
Treatment with ubidecarenone did not affect the absorption and distribution of the S- and R-enantiomers of warfarin, but produced a significant increase in the total serum clearance values of both R- and S-warfarin in rats.

Pharmacokinetics of the enantiomers of acenocoumarol in man.

The results indicate that the greater anticoagulant potency of R(+) compared with S(-) acenocoumarol can be explained mainly by stereoselective differences in their metabolic clearance.

Steady-state clearance rates of warfarin and its enantiomers in therapeutically dosed patients.

Differences in the clearance of R- and S-warfarin are demonstrated compared to the values derived from steady-state AUC data using patients with proven compliance and therapeutic doses.

Protein binding of warfarin enantiomers in serum of humans and rats

S(−)-Warfarin is eliminated more rapidly than the R(+) enantiomer in man, while the opposite occurs in rats, helping to explain the strong correlation in the elimination kinetics of the two enantiomers in individual rats.



Kinetics of warfarin absorption in man

The rate of warfarin absorption was rapid as guided by a consideration of the oral plasma concentration time curve in 8 subjects; peak drug concentrations in plasma were reached by 25 to 60 minutes after oral dosing.

The plasma half lives and the pharmacological effect of the enantiomers of warfarin in rats.

Kinetics of pharmacologic effects in man: The anticoagulant action of warfarin

The prothrombinopenic effect of warfarin as a function of time after drug administration can be predicted effectively by use of a mathematical relationship based on the dose or the initial concentration of the drug, the rate constants forwarfarin elimination and for prothROMbin complex activity decline, and the slope of the log‐plasma concentration‐response plot for the drug.

Blood Levels of Drug at the Equilibrium State after Multiple Dosing

THERE is ample evidence1–20 that when a fixed dose of drug is administered in a fixed multiple-dose regimen, the blood levels of drug eventually reach a steady state in which the blood level time

Kinetics of pharmacolog:c effects in man: The anticoagulant action of warfarin, CLIN

  • 1969

Studies on the 4-hydroxy coumarins. XVII. The resolution and absolute configuration of warfarin

  • J. Am. Chem. Soc
  • 1961

Stereochemi - cal considerations of the metabolism of warfarin in man : Studies with the Rand S isomers