Hall S D, Rudy A C, Knight P M, Brater D C
Department of Medicine, Indiana University School of Medicine, Wishard Memorial Hospital, Indianapolis 46202.
Clin Pharmacol Ther. 1993 Apr;53(4):393-400. doi: 10.1038/clpt.1993.42.
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.
已有研究提出布洛芬（R）-对映体在体循环前转化为（S）-对映体，但尚未在人体中直接进行检测。我们研究了10名健康志愿者体内布洛芬对映体的生物利用度。低剂量消旋布洛芬（400毫克）以随机顺序口服和静脉注射（60分钟输注）。对于（R）-和（S）-布洛芬，曲线下面积值、终末速率常数、清除率、代谢产物形成清除率以及血清蛋白结合率的口服剂量和静脉注射剂量之间均无显著差异。（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。采用两种方法（稳定同位素法和尿代谢产物的立体化学组成法）测定（R）-布洛芬的转化分数，两种方法对口服给药（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）的转化估计值相似。我们得出结论，布洛芬两种对映体的生物利用度均完全，且未发现体循环前显著转化的证据。
