Effects of aspirin on 14C-pirprofen disposition in rats

The effects of aspirin on 14C-pirprofen disposition in the rat were studied. An oral 60-mg/kg dose of aspirin significantly reduced plasma radioactivity during the 1--8-hr interval after an intravenous 5-mg/kg injection of 14C-pirprofen. The aspirin-treated group had only 69% as much area under the radioactivity curve as the control group. The radioactive material in plasma consisted almost entirely of 14C-pirprofen, as shown by GLC. The plasma clearance of 14C-pirprofen was 7.4 ml/hr for the aspirin-treated group and 5.1 ml/hr for the control group, while the volumes of distribution were 0.32 and 0.20 liter/kg, respectively. The apparent elimination half-life was unchanged at 5.9 hr. 14C-Pirprofen was approximately 98.6% bound to plasma proteins, and the binding decreased to an average of 97.2% in the presence of salicylate. Binding to blood cellular constituents was insignificant. Rats give 14C-pirprofen by intravenous injection without aspirin secreted 36.0--42.8% of the dose radioactivity into bile during 4 hr while a comparable group given 60 mg of aspirin/kg secreted 46.4--70.8%. TLC and GLC demonstrated that the radioactivity in rat bile was 80--90% conjugated 14C-pirprofen. The increased radioactive material secretion into bile was compensated in the intact rat by reabsorption, since the total radioactive material excreted in urine was not changed by aspirin administration.