title: Gender affects doxorubicin pharmacokinetics in patients with normal liver biochemistry.
abstract: We studied the variability in doxorubicin pharmacokinetics in 27 patients, all of whom had normal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography (HPLC). The relationship of doxorubicin clearance (dose/AUC) with biochemical tests (AST, bilirubin, alkaline phosphatase, albumin, creatinine) and physical characteristics (age, gender, height, weight, tumour type) was investigated. The 6 men had a significantly higher doxorubicin clearance than did the 21 women (median values, 59 and 27 lh-1 m-2, respectively; P = 0.002). Doxorubicin clearance was significantly lower in patients with breast cancer than in those with other tumours (median values, 26 and 53 lh-1 m-2, respectively; P = 0.0008). The other biochemical and physical parameters did not correlate with doxorubicin clearance. However, in multivariate analysis, gender was the only factor predicting doxorubicin clearance (r2 = 40%). The ratio of the AUCs for doxorubicinol and doxorubicin (R) was higher in the men than in the women (median values, 0.62 and 0.36, respectively; P = 0.03). We conclude that gender may be an important determinant of doxorubicin clearance in patients with normal liver biochemistry.
authors.affiliation: Imperial Cancer Research Fund Clinical Oncology Unit, United Medical School, Guy's Hospital, London, UK.
authors.forename: N A
authors.initials: NA
authors.lastname: Dobbs
authors.forename: C J
authors.initials: CJ
authors.lastname: Twelves
authors.forename: H
authors.initials: H
authors.lastname: Gillies
authors.forename: C A
authors.initials: CA
authors.lastname: James
authors.forename: P G
authors.initials: PG
authors.lastname: Harper
authors.forename: R D
authors.initials: RD
authors.lastname: Rubens
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D012727:Sex Characteristics
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin