Clinical pharmacokinetics and metabolism of paclitaxel after a three-hour infusion: comparison of two preparations

The clinical pharmacokinetics (PHK) of paclitaxel (PACLI) and its hydroxylated metabolites after three hours IV infusion (200 mg/m2) of two preparations were investigated in 13 patients receiving chemotherapy against breast cancer. Standard TaxolÒ was purchased from Bristol Myers Squibb and a test preparation ebetaxel (containing additional 2 mg/mL citric acid) was provided by Ebewe Pharma Austria. In the first cycle, either standard or test preparation was administered, then its alternative preparation in the second cycle (latin square, paired crossover design). In both treatment schedules the peak concentrations of PACLI occurred at the end of infusion after three hours. Mean peak concentration of PACLI was cmax5 505191131 ng/mL for the test preparation and cmax5 526991109 ng/mL for the standard preparation. No statistically significant differences in these plasma concentrations could be calculated. Mean tmax of metabolites was between 3.00 and 3.25 hours, their plasma concentrations were very similar: 6-OH-PACLI: cmax 4689266 ng/mL versus 4529212 ng/mL, 3Í-OH-PACLI: cmax 85938 ng/mL versus 90944 ng/mL, 3Í,6-DiOH-PACLI: cmax 87927 ng/mL versus 76931 ng/mL. The PHK parameters of PACLI (AUC, Cltot, Vd) and its metabolites (AUC, t1/2 dis, t1/2 el) did not differ significantly between both preparations. Biotransformation of PACLI into its three hydro-xylated metabolites (expressed as their appearance in blood) was not affected by the content of citric acid in the test preparation.