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. 1990;27(3):219-25.
doi: 10.1007/BF00685716.

Doxorubicin and doxorubicinol: intra- and inter-individual variations of pharmacokinetic parameters

J M Jacquet  1 , F Bressolle, M Galtier, M Bourrier, D Donadio, J Jourdan, J F Rossi
Affiliations

Doxorubicin and doxorubicinol: intra- and inter-individual variations of pharmacokinetic parameters

J M Jacquet et al. Cancer Chemother Pharmacol. 1990.

Abstract

Doxorubicin was given by short i.v. infusion (dose range 25-72 mg/m2) to 18 patients who underwent three to seven successive courses of chemotherapy (total, 57 courses). Plasma levels of doxorubicin and its major metabolite doxorubicinol were determined by high-performance liquid chromatography over a 48-h period after the infusion. Pharmacokinetic parameters for the parent drug and its metabolite were calculated for each course of treatment. The results show considerable inter- and intraindividual variations for most parameters. The coefficients of variation (CV) ranged from 37% to 93% (inter-individual) and from 6% to 59% (intra-individual). Nevertheless, we observed a good stability over successive courses for terminal half-life in six patients (CV, 6%-25%) and for clearance and AUC in four subjects (CV, 10%-22%). The ratio of the AUCs for doxorubicinol: doxorubicin averaged 0.514. The pharmacokinetic pattern of doxorubicinol was biphasic in plasma of the majority of patients. We propose a model for curve-fitting of these metabolite plasma concentrations that is based on two successive releases of the compound in the plasma compartment, separated by a lag time.

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