Pulmonary inversion of 2-arylpropionic acids: influence of protein binding.
Pulmonary inversion of 2-arylpropionic acids: influence of protein binding.
复制标题
2-芳基丙酸的肺反转：蛋白质结合的影响。
作者：
Hall,SD;Hassanzadeh-Khayyat,M;Knadler,MP;Mayer,PR
肺代谢对 2-芳基丙酸非甾体抗炎药推定首过代谢的可能贡献尚未有记录。用 4.5% 牛血清白蛋白或 5% 右旋糖酐灌注的离体灌注兔肺用于研究 (R)- 和 rac-布洛芬、非诺洛芬和氟比洛芬的肺部消除。在没有蛋白质结合的情况下，布洛芬通过反转和其他途径代谢，而非诺洛芬代谢基本上仅限于(R)-对映体的反转； (R)-布洛芬的倒数分数 (± SE) 为 0.37 ± 0.05，(R)-非诺洛芬的倒数分数 (± SE) 为 0.85 ± 0.03。在蛋白质存在的情况下，布洛芬和非诺洛芬都不会被代谢。在任何研究条件下，氟比洛芬均未经过肺部消除。这项研究表明，即使组织能够代谢，特别是 2-芳基丙酸的转化，但在存在这些药物特有的高度蛋白质结合的情况下，这种消除途径的定量重要性可能很小。 © 1992 Wiley-Liss, Inc.
The possible contribution of pulmonary metabolism to the putative first‐pass metabolism of 2‐arylpropionic acid nonsteroidal antiinflammatory drugs has not been documented. Isolated perfused rabbit lungs, perfused with 4.5% bovine serum albumin or 5% dextran, were used to study the pulmonary elimination of (R)‐ and rac‐ibuprofen, fenoprofen, and flurbiprofen. In the absence of protein binding, ibuprofen was metabolized via inversion and other pathways, whereas fenoprofen metabolism was essentially restricted to inversion of the (R)‐enantiomer; fraction inverted (± SE) was 0.37 ± 0.05 for (R)‐ibuprofen and 0.85 ± 0.03 for (R)‐fenoprofen. In the presence of protein, neither ibuprofen nor fenoprofen was metabolized. Flurbiprofen did not undergo pulmonary elimination under any condition studied. This study illustrates that even though a tissue is capable of metabolism, particularly inversion of 2‐arylpropionics, the quantitative importance of such elimination pathways may be minimal in the presence of the high degree of protein binding that is characteristic of these drugs. © 1992 Wiley‐Liss, Inc.