Possible active transport mechanism in pharmacokinetics of flunixin-meglumin in rabbits

The plasma and urine kinetics of flunixin-meglumin (FNX, 2 mg/kg, i.v.) in rabbits were examined. Unusual pharmacokinetic profiles were obtained, incl uding high binding percentage with plasma protein (> 99%), a short eliminat ion half-life (< 4 hr) and a relatively large Vd-area (0.5 L/kg). These pro files indicate that some active transport mechanisms are involved in FNX di sposition. The recovery of FNX from urine was approximately 9 % of the dose within 24 hr following the injection. The estimated renal clearance of the unbound drug nearly corresponded to the renal blood flow rates, indicating that active tubular secretion in the renal re-absorptive tract may be invo lved in the disposition. The effect of a concomitant administration of prav astatin (PV) on FNX disposition was also examined. PV is a representative s ubstrate of a transporter in human liver cells (OATP-2). After the PV admin istrations, the Vd-area of FNX and total body clearance markedly decreased, indicating that FNX is actively taken up and metabolized in liver cells by an OATP-2 like transporter. In conclusion, there are at least 2 active tra nsport pathways for FNX pharmacokinetics in rabbits, one is renal tubular s ecretion and the other is in the sinusoidal section of the liver.