Pharmacokinetic Equivalence of Taxotere and SID530, a Novel Docetaxel Formulation Containing Hydroxypropyl-beta-cyclodextrin in Monkeys

Abstract

SID530 is a new parenteral formulation of docetaxel containing hydroxypropyl-beta-cyclodextrin (HP-β-CD). In this study, a comparative pharmacokinetic study of 2 docetaxel parenteral solutions, SID530 and Taxotere, was carried out. In a crossover experimental design, 6 male cynomolgus monkeys received each formulation by intravenous infusion of a single dose. The concentration of docetaxel in whole blood and plasma was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The 2 formulations showed similar pharmacokinetic parameters in both whole blood and plasma, and displayed comparable values for maximum serum concentration (C_max), time to peak concentration (T_max), and area under the concentration-time curve (AUC). The 90% confidence intervals for the ratios of C_max and AUC values for SID530 to Taxotere were within the acceptable range of 0.80–1.20 in both plasma and whole blood. These findings indicate that SID530 and Taxotere are comparable in terms of their distribution in the blood and their plasma profile; consequently, these drugs are bioequivalent in the monkey.

Key words

docetaxel - bioequivalence - HP-β-CD - polysorbate 80 - LC-MS/MS

*

^*  These 2 authors contributed equally to this work.

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