Pharmacokinetic study of paclitaxel as a 3-hour infusion in an Indian population: 135 mg/m(2) vs. 175 mg/m(2)

The objective of this clinical study was to determine the pharmacokinetic p arameters of paclitaxel at doses of 135 and 175 mg/m(2) when given as a 3-h our infusion in an Indian population. Twelve cancer patients of both sexes participated in the study and a parallel experimental design was adopted fo r the assignment of doses to patients. A solid phase extraction technique w as used for sample clean-up followed by a reversed phase HPLC assay for the analysis of paclitaxel in plasma samples. Pharmacokinetic parameters such as C-max, AUC(0 --> infinity), T-1/2 beta, AUMC(0 --> infinity), V-SS, V-Z and CLT were determined by a compartment model-independent method using a P CNONLIN package. T-eff and AUC(eff) were also calculated and compared at th e two doses considering a plasma concentration of greater than or equal to0 .05 muM as threshold. The mean C-max and AUC(0 --> infinity) values were 2. 57 muM and 12.06 muM at the 135 mg/m(2) dose level while at the 175 mg/m(2) dose the values increased to 4.96 muM and 9.52 muM.h/l, respectively. it w as found that the 135 mg/m(2) dose resulted in greater mean CLT and V-SS va lues than the 175 mg/m(2) dose. The disposition of paclitaxel was found to be nonlinear and the pertinent pharmacokinetic parameters were comparable w ith other drugs should be undertaken cautiously, taking into consideration its nonlinear pharmacokinetics which necessitate proper adjustment of the i nfusion schedule and/or dose to avoid any adverse consequences to the patie nt. (C) 2001 Prous Science. All rights reserved.