Abstract

The pharmacokinetics and metabolism of Taxotere have been studied after intravenous infusion in mice, dogs and cancer patients. Multiphasic disposition profiles have been observed with rapid initial tissue uptake and large distribution volumes. Hepatobiliary extraction is the major route of elimination, with similar metabolic pathways in all the species. In mice, both systemic and tumour exposures increased proportionately with the dose. In phase I studies, Taxotere pharmacokinetics were not dependent on the various administration schedules. After short intravenous infusions of 70-115 mg/m2 every 3 weeks, a three phase disposition profile was observed with a terminal half-life of 12 hours and a plasma clearance of 21 l/hr/m2. A limited sampling strategy has been designed and large scale prospective population pharmacokinetic/pharmacodynamic studies have been implemented in ongoing phase II studies.