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

Pharmacokineticsand Drug Metabolism Unit, Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria, Austrian Society of Applied Pharmacokinetics, Vienna, Austria

Johannes Schueller

Department of Oncology and Internal Medicine, Hospital Rudolf-stiftung, Vienna, Austria

Heinz Schnait

Ebewe Pharma, Unterach/Attersee, Austria

Beate Springer

Department of Oncology and Internal Medicine, Hospital Rudolf-stiftung, Vienna, Austria

Isabella Eder

Austrian Society of Applied Pharmacokinetics, Vienna, Austria

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 c_max5 505191131 ng/mL for the test preparation and c_max5 526991109 ng/mL for the standard preparation. No statistically significant differences in these plasma concentrations could be calculated. Mean t_max of metabolites was between 3.00 and 3.25 hours, their plasma concentrations were very similar: 6-OH-PACLI: c_max 4689266 ng/mL versus 4529212 ng/mL, 3Í-OH-PACLI: c_max 85938 ng/mL versus 90944 ng/mL, 3Í,6-DiOH-PACLI: c_max 87927 ng/mL versus 76931 ng/mL.

The PHK parameters of PACLI (AUC, Cl_tot, Vd) and its metabolites (AUC, t_1/2 dis, t_1/2 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.

Key Words: metabolism • paclitaxel • pharmacokinetics • test preparation

Journal of Oncology Pharmacy Practice, Vol. 9, No. 4, 129-139 (2003)
DOI: 10.1191/1078155203jp113oa


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