卡铂对肿瘤患者的药物动力学与药效学

Clinical pharmacokinetic and pharmacodynamic studies of carboplatin in the patients with cancer

目的:研究国产卡铂(CBP)的临床药物动力学与药效学,方法:12例肿瘤病人iv gtt CBP 400mg,用反相HPLC法测定血清CBP浓度,并按残数法拟合药物动力学模型和参数.结果:12例肿瘤病人iv gtt CBP结束时的平均血药浓度(?).为55.10±13.00)mg/L,消除半衰期(T._(2?))为(143.09±49.36)min,清除率(CL)为(45.17±16.68)ml min.有效组和无效组的(?)分别为(61.03±9.28)和(52.14±12.77)mg/L,T_(?)分别为(191.27±26.92)和(119.00±35.31)min(P<0.01),CL分别为(31.42±6.79)和(52.04±15.97)ml/min(P<0.05).在2～10h内.有效组血清CBP浓度高于无效组(P<0.05).结论:肿瘤病人iv gtt CBP的血药浓度存在明显个体差异,且疗效与血药浓度和清除快慢有关.

AIM: To study the clinical pharmacokinetics and pharmacodynamics of carboplatin. METHODS: Twelve patients with cancer were treated with carboplatin 400 mg in 10% glucose injection 250 ml intravenous drip for 60 min. Serum levels of carboplatin were determined by reversed-phase high performance liquid chromatography. The data were processed with method of residuals. RESULTS: The average serum levels of carboplatin (c) was (55. 10±13. 00)mg/L at the end of intravenous drip. The half-life (T1/2β) of carboplatin was (143. 09 ± 49.36)min. The clearance (CD was (45. 17± 16. 68)ml/min. The average of c were (61.03 ± 9.28) and (52. 14 ± 12. 77 ) mg/L , T1/2β(191. 27 ± 26. 92 ) and (119.00 ± 35. 31)min (P<0. 01), and CL (31.42±6.79) and (52. 04 ± 15. 97)ml/min (P<0. 05) in effective and ineffective groups, respectively. After intravenous drip, the serum levels of carboplatin in effective group were higher than ineffective one from 2 to 10 hours (P< 0. 05). CONCLUSION: The individual variation of serum levels of carboplatin is shown significantly in patients with cancer after intravenous drip. The therapeutic effects of carboplatin is related with its serum levels and parameters of elimination.