Dobbs N A, Twelves C J, Gillies H, James C A, Harper P G, Rubens R D
Imperial Cancer Research Fund Clinical Oncology Unit, United Medical School, Guy's Hospital, London, UK.
Cancer Chemother Pharmacol. 1995;36(6):473-6. doi: 10.1007/BF00685796.
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.
我们研究了27例患者阿霉素药代动力学的变异性，所有患者的肝脏生化检查均正常。在单次静脉推注阿霉素的第一个周期后采集血样，并通过高效液相色谱法（HPLC）测定血浆水平。研究了阿霉素清除率（剂量/AUC）与生化检查（谷草转氨酶、胆红素、碱性磷酸酶、白蛋白、肌酐）和身体特征（年龄、性别、身高、体重、肿瘤类型）之间的关系。6名男性的阿霉素清除率显著高于21名女性（中位数分别为59和27 lh-1 m-2；P = 0.002）。乳腺癌患者的阿霉素清除率显著低于其他肿瘤患者（中位数分别为26和53 lh-1 m-2；P = 0.0008）。其他生化和身体参数与阿霉素清除率无关。然而，在多变量分析中，性别是预测阿霉素清除率的唯一因素（r2 = 40%）。男性阿霉素醇与阿霉素的AUC比值（R）高于女性（中位数分别为0.62和0.36；P = 0.03）。我们得出结论，对于肝脏生化正常的患者，性别可能是阿霉素清除率的重要决定因素。
