Pharmacokinetics and metabolism of doxorubicin after short-term infusions in lymphoma patients.
OBJECTIVE
Twenty-four patients (17 males and 7 females with a mean age of 54 years) with malignant lymphoma participated in a study of doxorubicin pharmacokinetics after 50 mg/m(2) as 10-min infusions. In addition to plasma samples, serial leukocyte samples and - in one subject - serial biopsy specimens from lymphoma infiltrates were obtained. The samples were analysed by reversed-phase high-performance liquid chromatography.


RESULTS
In contrast to several previous studies, the data suggested that 7-deoxydoxorubicinolone, and not doxorubicinone, is a metabolite of doxorubicin in humans. Doxorubicin, but no metabolites, was present in significant and fairly constant concentrations in circulating leukocytes. These levels may reflect the drug levels in lymphoma infiltrates. The data further suggest that metabolism to 7-deoxydoxorubicinone is subject to large interindividual variation, 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.
Andersen
A
A
Section for Clinical Pharmacology, Central Laboratory, The Norwegian Radium Hospital, Box 50, Montebello, 0310 Oslo, Norway. anders.andersen@klinmed.uio.no
Holte
H
H
Slørdal
L
L
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001711:Biotransformation; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008223:Lymphoma / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009279:Naphthacenes / Q000097:blood; D013997:Time Factors
D009279:Naphthacenes; D004317:Doxorubicin; C010013:adriamycinol; C049326:7-deoxyadriamycin aglycone