GENDER AFFECTS DOXORUBICIN PHARMACOKINETICS IN PATIENTS WITH NORMAL LIVER BIOCHEMISTRY

We studied the variability in doxorubicin pharmacokinetics in 27 patie nts, all of whom had normal liver biochemistry tests. Blood samples we re collected after the first cycle of single-agent doxorubicin given a s an i.v. bolus and plasma levels were measured by high-performance li quid chromatography (HPLC). The relationship of doxorubicin clearance (dose/AUC) with biochemical tests (AST, bilirubin, alkaline phosphatas e, albumin, creatinine) and physical characteristics (age, gender, hei ght, weight, tumour type) was investigated. The 6 men had a significan tly higher doxorubicin clearance than did the 21 women (median values, 59 and 27 lh(-1) m(-2), respectively, P = 0.002). Doxorubicin clearan ce was significantly lower in patients with breast cancer than in thos e with other tumours (median values, 26 and 53 lh(-1) m(-2), respectiv ely; P = 0.0008). The other biochemical and physical parameters did no t correlate with doxorubicin clearance. However, in multivariate analy sis, gender was the only factor predicting doxorubicin clearance (r(2) = 40%). The ratio of the AUCs for doxorubicinol and doxorubicin (R) w as 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 d eterminant of doxorubicin clearance in patients with normal liver bioc hemistry.