Pharmacokinetics of paclitaxel in an anephric patient

Purpose: To assess the pharmacokinetics of paclitaxel for recurrent Wilms' tumor in an anephric pediatric patient receiving hemodialysis. Methods: Pac litaxel was administered at a dose of 250 mg/m(2) and 350 mg/m(2) by 24-h c ontinuous intravenous (IV) infusion as two consecutive courses, respectivel y, separated by approximately 3 weeks. Paclitaxel plasma concentrations wer e measured by high-performance liquid chromatography (HPLC). Results: Pacli taxel disposition was comparable to that reported in similarly treated chil dren with normal renal function. For the first course (250 mg/m(2)), paclit axel concentrations were best fit by a two-compartment, first-order model. The calculated pharmacokinetic parameters were 0.312 h(-1) for the first-or der rate constant of elimination (K-e), 52.4 l/m(2) for the apparent volume of distribution (V-e), 0.170 h(-1) and 0.105 h(-1) for the first-order rat e constants for transit from central to peripheral compartments (K-cp) and peripheral to central compartments (K-pc), respectively, 16.9 mu M.h for th e area under the plasma concentration-versus-time curve (AUC), and 273 ml/m in per m(2) for average clearance (Cl). The concentration-versus-time data with the second course (at the higher dosage of 350 mg/m(2)) were better de scribed by a two-compartment model with saturable elimination. The calculat ed pharmacokinetic parameters were 12.0 mu mol.h(-1) for the maximal rate o f elimination (Vm(1-0)), 0.158 mu M for the concentration at which the rate of elimination is 50% of maximal (Km(t-0)), 0.809 h(-1) for K-cp, 0.0792 h (-1) for K-pc, 23.5 l/m(2) For V-c, 20.9 mu M.h for AUG, and 327 ml/min per m(2) For Cl. Paclitaxel was undetectable in the dialysate. Conclusions: Th e level of systemic exposure in our anephric patient was comparable to or l ower than that achieved in patients with normal renal function at similar d osages. The patient tolerated therapy without problems. It appears that ped iatric patients in renal failure call be treated with paclitaxel as a 24-h continuous infusion at doses similar to those used in patients with normal renal function.