PULMONARY INVERSION OF 2-ARYLPROPIONIC ACIDS - INFLUENCE OF PROTEIN-BINDING

被引:21
作者
HALL, SD
HASSANZADEHKHAYYAT, M
KNADLER, MP
MAYER, PR
机构
[1] INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202
[2] PURDUE UNIV,SCH PHARM,DEPT IND & PHYS PHARM,W LAFAYETTE,IN 47907
关键词
IBUPROFEN; FENOPROFEN; FLURBIPROFEN; RABBIT LUNG; 1ST-PASS; PRESYSTEMIC;
D O I
10.1002/chir.530040604
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:349 / 352
页数:4
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