LACK OF PRESYSTEMIC INVERSION OF (R)-IBUPROFEN TO (S)-IBUPROFEN IN HUMANS
LACK OF PRESYSTEMIC INVERSION OF (R)-IBUPROFEN TO (S)-IBUPROFEN IN HUMANS
复制标题
DOI：
10.1038/clpt.1993.42
复制
发表时间：
1993-04-01
影响因子：
6.7
通讯作者：
BRATER, DC
中科院分区：
文献类型：
--
作者：
HALL, SD;RUDY, AC;BRATER, DC
已经提出了（R）-布洛芬向（S）-布洛芬的系统前转化，但未在人体中直接检测。我们研究了布洛芬对映体在10名健康志愿者体内的生物利用度。以随机顺序口服和静脉注射（60分钟输注）低剂量外消旋布洛芬（400 mg）。对于（R）-和（S）-布洛芬的曲线下面积值、终末速率常数、清除率、代谢产物形成清除率和血清蛋白结合率，口服和静脉给药之间无显著差异。（R）-布洛芬和总布洛芬的生物利用度分别为0.92 ± 0.11和0.95 ± 0.08。用两种方法测定了（R）-布洛芬的分数转化率（稳定同位素法和尿液代谢物的立体化学组成），得出了类似的经口给药转化估计值（分别为0.56 +/- 0.12和0.60 +/- 0.07）和静脉给药（分别为0.56 +/- 0.09和0.60 +/- 0.06）。我们得出结论，布洛芬的两种对映体的生物利用度是完整的，没有发现显着的系统前转化的证据。
Presystemic inversion of (R)- to (S)-ibuprofen has been proposed but not directly examined in humans. We investigated the bioavailability of the enantiomers of ibuprofen in 10 healthy volunteers. Low-dose racemic ibuprofen (400 mg) was administered orally and intravenously (60-minute infusion), in random order. There were no significant differences between oral and intravenous doses for the area under the curve values, terminal rate constants, clearances, metabolite formation clearances, and serum protein binding for (R)- and (S)-ibuprofen. The bioavailabilities of (R)-ibuprofen and total ibuprofen were 0.92 +/- 0.11 and 0.95 +/- 0.08, respectively. The fractional inversion of (R) -ibuprofen was determined by two methods (stable isotope method and from the stereochemical composition of the urinary metabolites) that gave similar estimates of inversion for oral dosing (0.56 +/- 0.12 and 0.60 +/- 0.07, respectively) and intravenous dosing (0.56 +/- 0.09 and 0.60 +/- 0.06, respectively). We conclude that the bioavailability of both enantiomers of ibuprofen is complete and find no evidence of significant presystemic inversion.