What question did this study set out to answer?

To evaluate the stereoselective pharmacokinetic and metabolic interactions between sulfinpyrazone and the individual enantiomers of racemic warfarin in humans.

January 1, 1986Clinical Pharmacology & Therapeutics

The warfarin-sulfinpyrazone interaction: stereochemical considerations

View Full Paper

Ask AI

Bookmark

To evaluate the stereoselective pharmacokinetic and metabolic interactions between sulfinpyrazone and the individual enantiomers of racemic warfarin in humans.
Administered pseudoracemic warfarin (1:1 12C-R(+) and 13C-S(-)warfarin) to 6 healthy subjects before and during oral sulfinpyrazone treatment.
Analyzed serial blood and urine samples using gas chromatography-mass spectrometry (GC/MS), including a 15-day 14C-tracer mass-balance study in one subject.
Sulfinpyrazone markedly increased hypoprothrombinemia, significantly decreased the clearance of (S)-warfarin, and increased the clearance of (R)-warfarin.
Sulfinpyrazone decreased urinary excretion and increased fecal excretion of warfarin metabolites by equivalent amounts, fully accounting for the administered dose.
Enhanced anticoagulation occurs primarily via cytochrome P-450 inhibition of the potent (S)-warfarin, while increased (R)-warfarin clearance stems from plasma protein displacement.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Pharmacokinetic study reveals that sulfinpyrazone selectively inhibits (S)-warfarin clearance in healthy individuals, highlighting the stereochemical basis of increased anticoagulation.

Cite This Study

Toon et al. (1986) studied this question.

synapsesocial.com/papers/6a728968f44fa9f079dffae2 https://doi.org/10.1038/clpt.1986.3

View Full Paper

Ask AI

Bookmark

Implication

Pharmacokinetic study reveals that sulfinpyrazone selectively inhibits (S)-warfarin clearance in healthy individuals, highlighting the stereochemical basis of increased anticoagulation.

The warfarin-sulfinpyrazone interaction: stereochemical considerations

Key Points

Discussion

Implication

Cite This Study

The warfarin-sulfinpyrazone interaction: stereochemical considerations

Key Points

Discussion

Implication

Cite This Study