国产卡铂的临床药代动力学与药效学研究

STUDY ON THE CLINICAL PHARMACOKINETIC AND PHARMACODYNAMIC OF CARBOPLATIN IN THE PATIENTS WITH CANCER

目的研究国产卡铂（ＣＢＰ）的临床药代动力学与药效学。方法１２例肿瘤病人静滴ＣＢＰ４００ｍｇ。用反相高效液相色谱法测定血清ＣＢＰ浓度；按１９７８年常州会议制定的标准作疗效评定。结果静滴结束时的平均血药浓度（Ｃｏ）为５４．７９±１１８１ｍｇ．ｍｌ－１，消除半衰期（Ｔ１／２β）为１４３．１２±４９．４１ｍｉｎ。有４例部分缓解（ＰＲ），８例稳定（ＮＣ）或进展（ＰＤ）。有效组（ＰＲ）和无效组（ＮＣ＋ＰＤ）的Ｃｏ分别为６１．０３±９．２８和５２．１４±１２．７７ｍｇ．Ｌ－１，Ｔ１／２β分别为１９１．２７±２６．９２和１１９．００±３５．３１ｍｉｎ（Ｐ＜０．０１）。在２～１０ｈ内，有效组血清ＣＢＰ浓度高于无效组（Ｐ＜０．０５）。结论肿瘤病人静滴ＣＢＰ的血药浓度存在明显个体差异。

Objective:To study the clinical pharmacokinetics and pharmacodynamics of carboplatin.Methods:Serum carboplatin levels in 12 patients with cancer and being treated by intravenous drip of carboplatin were determined by reversed-phase HPLC.And responses to treatment were evaluated according to the criteria made at Changzhou Meeting in 1978.Results:The average serum carboplatin level(Co) was 54.79±11.81 mg.L -1 at the end of intravenous drip.The half-life(T 1/2β ) of carboplatin was 143.12±49.41 minutes.The outcome of carboplatin treatment was as follows:partial remission (PR) in 4 cases(33.3%),no change (NC) or progress of disease (PD) in 8 cases(66.7%).The average levels of Co were 61.03±9.28 and 52.14±12.77mg.L -1 ,and T 1/2β 191.27±26.92 and 119.00±35.31 minutes( P <0.01)in effective and ineffective groups,respectively.After intravenous drip,the serum carboplatin levels in effective group were higher than those in ineffective one from 2 to 10 hours ( P <0.05).Conclusion:The individual serum carboplatin levels vary significantly in patients with cancer after intravenous drip.The therapeutic effects of carboplatin is related to its serum levels and parameters of elimination.