布洛芬精氨酸注射及口服给药在大鼠体内的立体选择性药代动力学

利用手性高效液相色谱法研究大鼠注射及口服布洛芬精氨酸之后布洛芬对映体的药代动力学。布洛芬精氨酸注射及口服给药后, 布洛芬对映体的药代动力学呈现立体选择性, 且口服给药后立体选择性程度更高。与系统前转化相比, R-布洛芬至S-布洛芬的系统转化在口服给药后立体选择性药代动力学中起更重要的作用。布洛芬精氨酸口服给药后, 优势对映体S-布洛芬迅速吸收, S-布洛芬与R-布洛芬的绝对生物利用度分别为100% 和80%。基于研究发现的S-布洛芬体内系统性暴露, 可以推断布洛芬精氨酸注射及口服给药后的药理作用相似, 仅在作用的起始阶段存在差异。

Pharmacokinetics of ibuprofen enantiomers in rats after intravenous and oral administration of ibuprofen arginate

The pharmacokinetics of ibuprofen enantiomers were studied in rats after intravenous and oral administration of ibuprofen arginate by means of a chiral HPLC method.  The pharmacokinetics of ibuprofen was stereoselective after intravenous and oral administration of ibuprofen arginate.  The pharmacokinetic stereoselectivity was higher after oral administration than that after intravenous administration.  The systematic (R)-(−)-to-(S)-(+) inversion might be more important than the presystematic one in the stereoselective pharmacokinetics after oral administration.  Oral administration of ibuprofen arginate resulted in a very rapid absorption of (S)-(+)-ibuprofen (eutomer), and the absolute bioavailabilities of (S)-(+)-ibuprofen and (R)-(−)-ibuprofen were about 100% and 80%, respectively.  Based on the systemic exposure of (S)-(+)-ibuprofen, it could be concluded that the pharmacological actions might be similar when ibuprofen arginate was given orally and intravenously, except some differences in the onset of action.