布洛芬对映体在兔体内的药代动力学相互作用。

Pharmacokinetic interaction of ibuprofen enantiomers in rabbits.

作者信息

Lin Wenhui, Hayakawa Toru, Yanaguimoto Hitomi, Kuzuba Mamoru, Obara Takako, Ding Guohua, Cui Fude, Inotsume Nobuo

机构信息

Department of Pharmacology and Therapeutics, Hokkaido College of Pharmacy, Katsuraoka, Otaru 047-0264, Japan.

出版信息

J Pharm Pharmacol. 2004 Mar;56(3):317-21. doi: 10.1211/0022357022845.

DOI:10.1211/0022357022845

PMID:15025856

Abstract

The potential interaction between two ibuprofen enantiomers was studied after intravenous administration of R-(-)-, S-(+)- and racemic ibuprofen to rabbits. The total body clearance values calculated by compartmental model analysis (0.65 +/- 0.21 for R-(-)-ibuprofen and 0.63 +/- 0.34 for S-(+)-ibuprofen) after intravenous administration of the racemate of ibuprofen were significantly smaller than those of individual enantiomers (0.95 +/- 0.23 for R-(-)-ibuprofen and 1.03 +/- 0.23 for S-(+)-ibuprofen), indicating that the enantiomer-enantiomer interaction results in a mutual inhibition. The enantiomeric interaction in the pharmacokinetic behaviour of ibuprofen after racemic administration is considered to be a result of an alteration in the metabolic or excretion phase (or both) rather than stereoselective protein binding in the systemic distribution.

摘要

在给兔子静脉注射R-(-)-、S-(+)-布洛芬及消旋布洛芬后，研究了两种布洛芬对映体之间的潜在相互作用。通过房室模型分析计算得出，静脉注射布洛芬消旋体后，其总体清除率值（R-(-)-布洛芬为0.65±0.21，S-(+)-布洛芬为0.63±0.34）显著低于单个对映体的总体清除率值（R-(-)-布洛芬为0.95±0.23，S-(+)-布洛芬为1.03±0.23），这表明对映体-对映体相互作用导致了相互抑制。消旋给药后布洛芬药代动力学行为中的对映体相互作用被认为是代谢或排泄阶段（或两者）改变的结果，而非全身分布中立体选择性蛋白结合的结果。