Heimark L D, Toon S, Gibaldi M, Trager W F, O'Reilly R A, Goulart D A
Clin Pharmacol Ther. 1987 Sep;42(3):312-9. doi: 10.1038/clpt.1987.154.
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.
通过气相色谱/质谱法分析连续采集的血浆、尿液和粪便样本中的母体药物及其代谢产物，评估了磺吡酮对假消旋苯丙香豆素对映体的药代动力学和处置的影响。基本上，所有给药剂量都可被解释为母体药物、已知代谢产物或它们的缀合物。苯丙香豆素和7-羟基代谢产物是回收的主要物质。排泄到尿液中的所有与药物相关的物质都被广泛缀合。磺吡酮治疗既不影响苯丙香豆素产生的低凝血酶原血症，也未显著改变单个（R）-和（S）-对映体的血浆消除动力学。然而，在磺吡酮存在的情况下，观察到两种对映体在血浆中的游离分数明显增加，并且（S）-苯丙香豆素的7-羟基化受到抑制。本研究结果与先前关于磺吡酮与结构相似的香豆素抗凝剂华法林之间相互作用的研究结果形成对比。
