Pulmonary inversion of 2-arylpropionic acids: influence of protein binding.
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.
Hall
S D
SD
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Hassanzadeh-Khayyat
M
M
Knadler
M P
MP
Mayer
P R
PR
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005279:Fenoprofen / Q000378:metabolism*; D005480:Flurbiprofen / Q000378:metabolism*; D007052:Ibuprofen / Q000378:metabolism*; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D008968:Molecular Conformation; D011485:Protein Binding; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013237:Stereoisomerism
D012710:Serum Albumin, Bovine; D005480:Flurbiprofen; D005279:Fenoprofen; D007052:Ibuprofen