肿瘤患者个体差异对卡培他滨药物代谢动力学影响

目的:研究个体差异(性别、年龄、体表面积及体质量)对肿瘤患者体内卡培他滨的药代动力学的影响,为临床合理使用卡培他滨提供依据。方法:选取76例不同类型肿瘤患者为研究对象,餐后口服卡培他滨片0.6 g(0.15 g,4片)后进行多点采集血样,HPLC-MS/MS检测受试者给药后血浆中的卡培他滨及其活性代谢物5-氟尿嘧啶(5-FU)的血药浓度,Phoenix WinNonlin7.0软件计算卡培他滨和5-FU的药动学参数AUC 0-∞和C max,研究性别、年龄、体表面积及体质量与卡培他滨及5-FU药动学的相关性。结果:男性卡培他滨C max比女性高49%,卡培他滨AUC 0-∞及5-FU的C max和AUC 0-∞值在性别之间没有区别。受试者年龄(26~65岁)与卡培他滨C max负相关(P<0.05),而与卡培他滨AUC 0-∞及5-FU的AUC 0-∞和C max无相关性;不同体表面积(1.28~2.01 m 2)患者卡培他滨的AUC 0-∞和C max值无明显差异,而5-FU的AUC 0-∞和C max随着体表面积的增加而减少。不同体质量(45.0~83.0 kg)患者体内卡培他滨的AUC 0-∞和C max的值无明显差异,但5-FU的AUC 0-∞和C max差异具有统计学意义(P<0.05)。结论:现有研究对象结果显示不同的个体差异因素对于卡培他滨的药动学影响不同。其中,性别和年龄主要影响卡培他滨吸收,而体表面积和体质量是卡培他滨的代谢过程主要影响因素。

Effects of individual differences on the pharmacokinetics of capecitabine in cancer patients

AIM:To study the effects of individual differences(gender,age,body surface area,and body weight)on the pharmacokinetics of capecitabine in cancer patients in hoping of providing evidence for the rational use of capecitabine in clinic.METHODS:A total of 76 patients with various solid tumors were given a single dose of 0.6 g(0.15 g,4 tablets)capecitabine in postprandial and blood samples were collected at multiple time points.The plasma concentration of capecitabine and its active metablolite,5-fluorouracil(5-FU)were analyzed by HPLC-MS/MS and the pharmacokinetic parameters of the drugs were calculated by Phoenix WinNonlin7.0 software.RESULTS:Following oral administration,the C max values of capecitabine were 49%higher in males compared to those in females.There was no difference in capecitabine AUC 0-∞,5-FU C max,and 5-FU AUC 0-∞between males and females.There was a negative correlation between age(26-65 years old)and C max value of capecitabine,whereas no correlation in capecitabine AUC 0-∞,5-FU AUC 0-∞,and 5-FU with various ages;For the body surface area,there was no significant difference in the AUC 0-∞and C max of capecitabine in patients with different body surface areas(1.28-2.01 m 2),wheras the AUC 0-∞and C max of 5-FU had statistical significance(P<0.05).The values were up-regulated with the decrease of body surface area.Body weights(45.0-83.0 kg)had no effect on the AUC 0-∞and C max of capecitabine,whereas they had statistical correlation with AUC 0-∞and C max of 5-FU(P<0.05).CONCLUSION:The current data indicate that different factors affect the pharmacokinetics of capeitabine differently.Among the factors,gender and age mainly affect the absorption process and body surface area and weight mainly influence the metabolism of capeitabine.