Original article: Pharmacokinetics and metabolism of epirubicin administered as i.v. bolus and 48-h infusion in patients with advanced soft-tissue sarcoma

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Abstract
We have studied the pharmacokinetics of epirubicin after its administration in sarcoma patients either as an i.v. bolus or as a 48-h infusion (5 courses each; 9 patients in total). Bolus injection was followed by a three exponential decay in plasma, with half-lives of 2.43 min, 1.95 h and 21.7 h; 48-h infusions were characterized by the very rapid establishment of a plasma plateau concentration followed by a biexponential decay after stopping the infusion. Pharmacokinetic parameters such as total plasma clearance, total volume of distribution, mean residence time and elimination half-life were similar, irrespective of the duration of the administration. In contrast, the relative amounts of the metabolites of epirubicin were reduced when the drug was administered over 48 h; in particular, the plasma levels of epirubicin glucuronide never exceeded those of epirubicin, which always occur after bolus injection. This may result from a lower availability of epirubicin for metabolism. These results now require validation in a larger group of patients using a cross-over design.

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