Pharmacokinetics and metabolism of doxorubicin after short-term infusions in lymphoma patients

Purpose/Methods: Twenty-four patients (17 males and 7 females with a mean a ge of 54 years) with malignant lymphoma participated in a study of doxorubi cin pharmacokinetics after 50 mg/m(2) as 10-min infusions. In addition to p lasma samples, serial leukocyte samples and - in one subject - serial biops y specimens from lymphoma infiltrates were obtained. The samples were analy sed by reversed-phase high-performance liquid chromatography. Results: In c ontrast to several previous studies, the data suggested that 7-deoxydoxorub icinolone, and not doxorubicinone, is a metabolite of doxorubicin in humans . Doxorubicin, but no metabolites, was present in significant and fairly co nstant concentrations in circulating leukocytes. These levels may reflect t he drug levels in lymphoma infiltrates. The data further suggest that metab olism to 7-deoxydoxorubicinone is subject to large interindividual variatio n, possibly due to a genetic polymorphism, and that significant levels of a metabolic product which may be a doxorubicin glucuronide can be recovered from plasma of patients treated with doxorubicin.