신장장애 가토에서 파크리탁셀의 약물동태

Abstract

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±382) compared to that in rabbits with in moderate renal failure induced by folic acid (780±209 ng/ml • hr). The apparent volume of distribution (Vd) (0.008±0.002 L/kg) and the elimination rate constant () (0.09±0.025 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±0.004 L/kg, 0.12±0.03 hr1), but not significantly different compared with that in rabbits with moderate renal failure (0.010±0.003 L/kg, 0.10±0.026 hr1). Total body clearance (CL) of paclitaxel in rabbits with severe renal failure (0.97± 0.183 L/hr/kg) was significantly (p<0.05) slower than that in control rabbits (1.68±0.440 L/hr/kg), but not significantly different compared with that in rabbits with in moderate renal failure (1.28±0.311 L/hr/kg). The terminal half-life (t1/2) of paclitaxel in rabbits with severe renal failure (7.46±2.16 hr) was significantly (p<0.05) longer than that in control rabbits (5.75±1.44 hr), but not significantly different compared to that in rabbits with moderate renal failure rabbits (6.67±1.76 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.