Pharmacokinetics and metabolism of epirubicin administered as i.v. bolus and 48-h infusion in patients with advanced soft-tissue sarcoma.
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.
Robert
J
J
Fondation Bergonié, Bordeaux, France.
Bui
N B
NB
D000293:Adolescent; D000328:Adult; D000368:Aged; D015251:Epirubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D013997:Time Factors
D015251:Epirubicin