卡培他滨片剂在恶性肿瘤患者中的生物等效性研究

Bioequivalence of capecitabine tablets in cancer patients

目的评价国产卡培他滨片与原研卡培他滨片在恶性肿瘤患者体内的生物等效性。方法采用多中心、随机、开放、两周期、双交叉的餐后试验设计,84例可适用含卡培他滨片化疗方案的实体瘤患者随机分别口服国产与原研卡培他滨片剂,每周期服药1次,单次给药1250 mg·m^-2,按照体表面积计算向下调整至0.5 g的整倍数片剂,给药两周期间清洗期为12 h。用液相色谱-质谱(LC-MS/MS)法测定血浆中卡培他滨浓度,进行生物等效性研究。结果实体瘤患者餐后服用卡培他滨片受试制剂和参比制剂后的药代动力学参数如下:Cmax分别为(3940±2300),(4040±2900)ng·mL^-1;AUC0-t分别为(4820±1620),(4750±1700)h·ng·mL^-1;AUC0-∞分别为(4870±1680),(4970±1750)h·ng·mL^-1。2种药物的Cmax、AUC0-t、AUC0-∞的几何均数比相对应的90%置信区间均在80.00%~125.00%。结论恶性肿瘤患者餐后口服卡培他滨片受试制剂和参比制剂具有生物等效性,且受试制剂和参比制剂不良事件发生情况相似。

Objective To evaluate the bioequivalence of domestic capecitabine tablets and original capecitabine tablets in patients with malignant tumor. Method A multicenter, randomized, open-lable, two-period crossover study was conducted in cancer patients, 84 patients with solid tumors who were suitable for capecitabine chemotherapy were randomly given domestic and original capecitabine tablets, once a period, with a single dose of 1250 mg·m^-2. The actual dose was adjusted to multiple of 0.5 according to the body surface area. The cleaning period was 12 hours during two periods of administration. The concentration of capecitabine in plasma was detected by liquid chromatography-mass spectrometry(LC-MS/MS). Results After taking capecitabine tablets, the pharmacokinetic parameters for test and reference preparations after meal were as follows:Cmax were(3940±2300),(4040±2900)ng·mL^-1;AUC0-t were(4820±1620),(4750±1700)h·ng·mL^-1;AUC0-∞ were(4870±1680),(4970±1750)h·ng·mL^-1. The 90% confidence intervals of Cmax, AUC0-t and AUC0-∞ of the two drugs were in the range of 80.00%-125.00%.Conclusion The test and reference preparations of capecitabine tablets are bioequivalent in cancer patients after meal, and the incidence of adverse events is similar between the test and reference preparations.