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KMID : 0941820020120020091
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Korean Journal of Clinical Pharmacy
2002 Volume.12 No. 2 p.91 ~ p.95
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Pharmacokinetics of Paclitaxel in Rabbits with Renal Failure Induced by Folic Acid
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정은정
곽혜선/최준식/이진환/이수국
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Abstract
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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 (1030pm382) compared to that in rabbits with in moderate renal failure induced by folic acid (780pm209;ng/ml{cdot}hr). The apparent volume of distribution (Vd) (0.008pm0.002;L/kg) and the elimination rate constant (beta);(0.09pm0.025;hr^{-1}) of paclitaxel in rabbits with severe renal failure were significantly (p<0.05) smaller and slower respectively than those of control rabbits (0.016pm0.004;L/kg,;0.12pm0.03;hr^{-1}), but not significantly different compared with that in rabbits with moderate renal failure (0.010pm0.003;L/kg,;0.10pm0.026;hr^{-1}). total body clearance (CL) of paclitaxel in rabbits with severe renal failure (0.97pm0.183;L/hr/kg) was significantly (p<0.05) slower than that in control rabbits (1.68pm0.440;L/hr/kg), but not significantly different compared with that in rabbits with in moderate renal failure (1.28pm0.311;L/hr/kg). The terminal half-life (t_{1/2}) of paclitaxel in rabbits with severe renal failure (7.46pm2.16;hr) was significantly (p<0.05) longer than that in control rabbits (5.75pm1.44;hr), but not significantly different compared to that in rabbits with moderate renal failure rabbits (6.67pm1.76;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.
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