Doxorubicin and doxorubicinol: intra- and inter-individual variations of pharmacokinetic parameters.
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.
Jacquet
J M
JM
Laboratoire Universitaire de Thérapeutique, Faculté de Médecine, Montpellier-Nîmes, France.
Bressolle
F
F
Galtier
M
M
Bourrier
M
M
Donadio
D
D
Jourdan
J
J
Rossi
J F
JF
D000328:Adult; D000368:Aged; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007206:Individuality; D008297:Male; D008875:Middle Aged
D004317:Doxorubicin; C010013:adriamycinol