ENHANCED SYSTEMIC BIOAVAILABILITY OF INTRAVENOUS AND RECTAL PIROXICAMIN RABBITS FOLLOWING ORAL-ADMINISTRATION OF CHENODEOXYCHOLIC ACID

The effect of orally administered chenodeoxycholic acid on the systemi c bioavailability and pharmacokinetics of intravenous and rectal pirox icam was studied in rabbits. Intravenous injection of piroxicam into c henodeoxycholic acid pretreated rabbits resulted in a plasma piroxicam concentration significantly higher than that in rabbits receiving pir oxicam alone. A significant increase in the terminal elimination half- life t(1/2) (11.68 +/- 1.45 and 20.87 +/- 2.96 h for the control and t reated rabbits, respectively), a 44.01% decrease in the apparent elimi nation rate constant K and a 21.65% decrease in the systemic clearance (Cl) with chenodeoxycholic acid were obtained. Furthermore, a 28.58% increase in the area under the plasma concentration time curve (32.25 +/- 1.53 and 41.16 +/- 0.976 mu g.ml(-1).h(-1) for the control and tre ated rabbits, respectively) was also observed However, no significant difference in the apparent volume of distribution between both groups was noted (p < 0.05). Similar results were obtained in rabbits receivi ng piroxicam suppositories. The t(1/2) of piroxicam was increased from 16.86 +/- 1.92 to 29.50 +/- 3.65 h with chenodeoxycholic acid adminis tration. In addition, the mean area under piroxicam plasma level rime curves significantly increased while the values for K and Cl significa ntly decreased by chenodeoxycholic acid administration. The results in every case (intravenous and rectal administration) were explained on the bases of the increase in bile acid pool size and the enhancement i n the enterohepatic recycling of piroxicam by the chenodeoxycholic aci d.