The effect of sulfinpyrazone on the disposition of pseudoracemic phenprocoumon in humans.

Abstract

The effect of sulfinpyrazone on the pharmacokinetics and disposition of the enantiomers of pseudoracemic phenprocoumon was assessed by analyzing serial plasma, urine, and fecal samples for parent drug and metabolites by GC/MS. Essentially all of the administered dose could be accounted for either as parent drug, known metabolites, or their conjugates. Phenprocoumon and the 7-hydroxymetabolite represented the major materials recovered. All drug-related materials excreted into the urine were extensively conjugated. Sulfinpyrazone treatment did not affect the hypoprothrombinemia produced by phenprocoumon nor did it significantly alter the plasma elimination kinetics of the individual (R)- and (S)-enantiomers. However, an apparent increased free fraction of both enantiomers in plasma and inhibition of 7-hydroxylation of (S)-phenprocoumon were observed in the presence of sulfinpyrazone. The results of this study are contrasted with those of a previous study on the interaction between sulfinpyrazone and the structurally similar coumarin anticoagulant warfarin.

• Authors: L D Heimark, S Toon, M Gibaldi, W F Trager, R A O'Reilly, D A Goulart
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 42 Issue 3 Pg. 312-9 (Sep 1987) ISSN: 0009-9236 [Print] United States
• PMID: 3621786 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 4-Hydroxycoumarins
• Blood Proteins
• Phenprocoumon
• Sulfinpyrazone

Topics

• 4-Hydroxycoumarins (metabolism)
• Adult
• Blood Proteins (metabolism)
• Feces (analysis)
• Gas Chromatography-Mass Spectrometry
• Humans
• Hydroxylation
• Kinetics
• Male
• Phenprocoumon (analogs & derivatives, metabolism)
• Protein Binding
• Reference Values
• Stereoisomerism
• Sulfinpyrazone (pharmacology)