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: Paclitaxel was administered at a dose of 250 mg/m2 and 350 mg/m2 by 24-h continuous intravenous (IV) infusion as two consecutive courses, respectively, separated by approximately 3 weeks. Paclitaxel plasma concentrations were measured by high-performance liquid chromatography (HPLC). Results: Paclitaxel disposition was comparable to that reported in similarly treated children with normal renal function. For the first course (250 mg/m2), paclitaxel concentrations were best fit by a two-compartment, first-order model. The calculated pharmacokinetic parameters were 0.312 h−1 for the first-order rate constant of elimination (Ke), 52.4 l/m2 for the apparent volume of distribution (Vc), 0.170 h−1 and 0.105 h−1 for the first-order rate constants for transit from central to peripheral compartments (Kcp) and peripheral to central compartments (Kpc), respectively, 16.9 μM·h for the area under the plasma concentration-versus-time curve (AUC), and 273 ml/min per m2 for average clearance (Cl). The concentration-versus-time data with the second course (at the higher dosage of 350 mg/m2) were better described by a two-compartment model with saturable elimination. The calculated pharmacokinetic parameters were 12.0 μmol · h−1 for the maximal rate of elimination (Vm1−0), 0.158 μM for the concentration at which the rate of elimination is 50% of maximal (Km1−0), 0.809 h−1 for Kcp, 0.0792 h−1 for Kpc, 23.5 l/m2 for Vc, 20.9 μM·h for AUC, and 327 ml/min per m2 for Cl. Paclitaxel was undetectable in the dialysate. Conclusions: The level of systemic exposure in our anephric patient was comparable to or lower than that achieved in patients with normal renal function at similar dosages. The patient tolerated therapy without problems. It appears that pediatric patients in renal failure can be treated with paclitaxel as a 24-h continuous infusion at doses similar to those used in patients with normal renal function.