Abstract
The plasma and urine kinetics of flunixin-meglumin (FNX, 2 mg/kg, i.v.) in rabbits were examined. Unusual pharmacokinetic profiles were obtained, including high binding percentage with plasma protein (> 99%), a short elimination half-life (< 4 hr) and a relatively large Vd-area (0.5 L/kg). These profiles indicate that some active transport mechanisms are involved in FNX disposition. 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 involved in the disposition. The effect of a concomitant administration of pravastatin (PV) on FNX disposition was also examined. PV is a representative substrate of a transporter in human liver cells (OATP-2). After the PV administrations, 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 transport pathways for FNX pharmacokinetics in rabbits, one is renal tubular secretion and the other is in the sinusoidal section of the liver.
