Williams K M, Knihinicki R D, Day R O
Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Darlinghurst, N.S.W., Australia.
Agents Actions. 1991 Nov;34(3-4):381-6. doi: 10.1007/BF01988732.
The stereoselective disposition of ibuprofen was studied in male New Zealand White (NZW) rabbits (n = 4) following an infusion (0.16 mg/kg/min) to steady-state of each of the enantiomers of ibuprofen with one week between treatments. The mean (+/- SEM) steady-state clearances of (R)-ibuprofen (15.5 +/- 1.1 ml/min/kg) and (S)-ibuprofen (13.6 +/- 1.9 ml/min/kg) were not significantly different from each other (p greater than 0.05) and exceeded the plasma clearance of indocyanine green (4.3 +/- 0.4 ml/min/kg) in a separate group of rabbits (n = 6). When the infusion rate of the enantiomers was doubled there was a significant decrease in the mean clearance of both (R)-ibuprofen (28%; p less than 0.018) and (S)-ibuprofen (24%; p less than 0.003). There was enantiospecific chiral inversion of (R)-ibuprofen to (S)-ibuprofen (fi = 0.30 +/- 0.07) as has been observed in all species so far studied for this 2-arylpropionic acid. The metabolic capacity for elimination of ibuprofen enantiomers was much greater than reported for either fenoprofen or ketoprofen and suggests that the clearance of ibuprofen enantiomers may be flow dependent in this species.
在雄性新西兰白兔（NZW）（n = 4）中研究了布洛芬的立体选择性处置情况。对布洛芬的每种对映体以0.16 mg/kg/min的输注速率输注至稳态，两次治疗之间间隔一周。（R）-布洛芬的平均（+/- SEM）稳态清除率为（15.5 +/- 1.1 ml/min/kg），（S）-布洛芬的平均（+/- SEM）稳态清除率为（13.6 +/- 1.9 ml/min/kg），两者之间无显著差异（p>0.05），且超过了另一组兔子（n = 6）中吲哚菁绿的血浆清除率（4.3 +/- 0.4 ml/min/kg）。当对映体的输注速率加倍时，（R）-布洛芬的平均清除率显著降低（28%；p<0.018），（S）-布洛芬的平均清除率也显著降低（24%；p<0.003）。与迄今为止研究过的所有物种中观察到的该2-芳基丙酸情况一样，存在（R）-布洛芬向（S）-布洛芬的对映体特异性手性转化（fi = 0.30 +/- 0.07）。布洛芬对映体的代谢消除能力远大于报道的非诺洛芬或酮洛芬，这表明在该物种中布洛芬对映体的清除可能与血流有关。
