肿瘤患者单次和多次口服替吉奥片的药动学研究  

Single-Dose and Multiple-Dose Pharmacokinetic Study of Tegafur, Gimeracil, and Oteracil Potassium Tablets in Patients with Advanced Solid Tumors

作　　者：朱仲玲 薛津怀[1] 阎昭[1] 朱莉[2] 刘美君[1] 

机构地区：[1]天津医科大学附属肿瘤医院临床药理研究室 天津市肿瘤防治重点实验室,天津市300060 [2]天津医科大学附属肿瘤医院放疗科

出　　处：《中国肿瘤临床》2011年第10期594-597,共4页Chinese Journal of Clinical Oncology

摘　　要：目的:评价肿瘤患者单次和多次口服替吉奥片的药动学特征。方法:设单次给药组10例,给药剂量60 mg;连续给药组9例,每次给药剂量60 mg,1日2次,连续服用7d。采用液相色谱-串联质谱法测定血浆中替加氟及其代谢物5-氟脲嘧啶(5-FU)、吉美嘧啶(CDHP)和奥替拉西(Oxo)的浓度。采用DAS2.0药动学软件进行药动学参数的分析和计算。结果:单次给药替加氟C_(max)为(1407±383)ng·mL^(-1),AUC_(0-1)为(15 403±8439)ng·h·mL^(-1),活性代谢物5-氟脲嘧啶C_(max)为(128±36)ng·mL^(-1),AUC0-1为(539±138)ng·h·mL^(-1),吉美嘧啶C_(max)为(222±93)ng.mL^(-1),AUC_(0-1)为(962±390)ng·h·mL^(-1),奥替拉西C_(max)为(33.2±14.6)ng·mL^(-1),AUC_(0-1)为(117±64)ng·h·mL^(-1)与单次给药相比,多次给药后替加氟的C_(max)和AUC增加明显(P<0.05),但其增加程度与理论蓄积系数接近,而代谢物氟脲嘧啶、吉美嘧啶及奥替拉西的C_(max)和AUC无明显增加。受试者在研究期间未出现重度以上不良反应。结论:口服替吉奥片后,受试者耐受良好。多次给药后,替吉奥片主要成分的药代动力学行为没有发生明显变化。Objective： To study the single-dose and multiple-dose pharmacokinetics of tegafur, gimeracil, and oteracil potassium tablets in patients with advanced solid tumors. Methods： Ten patients for the single-dose pharmacokinetics study were administrated 60 mg of tegafur, gimeracil, and oteracil potassium tablets. Nine patients for the multiple-dose pharmacokinetics study were given 60 mg of tegafur, gimeracil, and oteraeil potassium tablets twice a day for seven consecutive days. The plasma concentrations of tegafur, 5-fluorouracil （ 5-FU ）, gimeracil （ CDHP ）, and oteracil potassium （ Oxo ） were determined using high-performance liquid chromatography-tandem mass spectrometry, DAS 2.0 was applied to assess the plasma concentration-time data, Results： After single-dose administration, the Cmax and AUC0-t of tegafur were （ 1407 ± 383 ） ng·mL-1 and （ 15403 ±8439 ） ng·mL-1 for 5-FU, （ 128 ±36 ） ng·mL-1 and （ 539 ± 138 ） ng·mL-1; for CDHP, （ 222 m 93 ）and （ 962± 390 ）ng·mL-1 and for Oxo, （ 33.2±14.6 ） ng·mL-1and （ 117 ±64 ）ng·mL-1. Comparing single-dose group with multiple-dose group, no significant differences were observed in the pharmacokinetics parameters of 5-FU, CDHP, and Oxo. With respect to tegafur, significant differences were observed in Cmax and AUC, but the increase in Cmax and AUC were close to accumulation coefficient. The toxicity of tegafur, gimeracil, and oteracil potassium tablets varied from mild to moderate. Grades 3 or 4 toxicity was not observed during the study. Conclusion： All participants had good tolerance throughout the study. After seven days of continuous administration, no significant differences were observed in the pharmacokinetic parameters of tegafur, 5-FU, CDHP, and Oxo.

关 键 词：替吉奥片 液相色谱-串联质谱法 药代动力学 肿瘤 

分 类 号：R969.1[医药卫生—药理学]