Pharmacokinetics of Paclitaxel in Rabbits with Renal Failure Induced by Folic Acid

신장장애 가토에서 파크리탁셀의 약물동태

The pharmacokinetics of intravenous paclitaxel (1 mg/kg) were investigated in rabbits with renal failure induced by folic acid. The area under the plasma concentration-time curve from time zero to time infinity (AUC) of paclitaxel was significantly (p<0.05) greater in rabbits with severe renal failure induced by folic acid $(1030\pm382)$ compared to that in rabbits with in moderate renal failure induced by folic acid $(780\pm209\;ng/ml{\cdot}hr)$. The apparent volume of distribution (Vd) $(0.008\pm0.002\;L/kg)$ and the elimination rate constant $(\beta)\;(0.09\pm0.025\;hr^{-1})$ of paclitaxel in rabbits with severe renal failure were significantly (p<0.05) smaller and slower respectively than those of control rabbits $(0.016\pm0.004\;L/kg,\;0.12\pm0.03\;hr^{-1})$, but not significantly different compared with that in rabbits with moderate renal failure $(0.010\pm0.003\;L/kg,\;0.10\pm0.026\;hr^{-1})$. total body clearance (CL) of paclitaxel in rabbits with severe renal failure $(0.97\pm0.183\;L/hr/kg)$ was significantly (p<0.05) slower than that in control rabbits $(1.68\pm0.440\;L/hr/kg)$, but not significantly different compared with that in rabbits with in moderate renal failure $(1.28\pm0.311\;L/hr/kg)$. The terminal half-life ($t_{1/2}$) of paclitaxel in rabbits with severe renal failure $(7.46\pm2.16\;hr)$ was significantly (p<0.05) longer than that in control rabbits $(5.75\pm1.44\;hr)$, but not significantly different compared to that in rabbits with moderate renal failure rabbits $(6.67\pm1.76\;hr)$. The above data could be at least partly decrease in due to paclitaxel excretion in rabbits with renal failure, since $7-15\%$ of interavenous paclitaxel was excreted via kidney as unchanged forms plus its metablites.