富马酸替诺福韦二吡呋酯片在健康国人体内的药动学及生物等效性研究  

Pharmacokinetics and bioequivalence of tenofovir disoproxil fumarate tablets in healthy Chinese volunteers

作　　者：宫旭[1] Imene Adouani 曾雪芳[1] 杭太俊[1] 宋敏[1] 

机构地区：[1]中国药科大学药物分析室,南京210009

出　　处：《中国新药杂志》2013年第6期686-690,共5页Chinese Journal of New Drugs

摘　　要：目的:建立人血浆中替诺福韦浓度的LC-MS/MS测定法,并用于富马酸替诺福韦二吡呋酯片的药动学和生物等效性研究。方法:采用自身双交叉试验设计,20例男性健康受试者随机分成2组,分别空腹口服受试制剂或参比制剂300 mg,0～72 h间隔采集血样。以LC-MS/MS法测定血浆替诺福韦浓度,DAS2.1.1计算药动学参数。结果:建立的LC-MS/MS法在2～1 200 ng.mL-1范围内线性关系良好,最低定量限为2 ng·mL-1,批内及批间精密度RSD均小于15%。受试制剂与参比制剂的Tmax均为(0.5±0.2)h,Cmax分别为(604±207)和(573±189)ng.mL-1,t1/2分别为(17.1±2.9)和(17.4±4.0)h,AUC0～72 h分别为(2 490±604)和(2 297±499)h·ng·mL-1。结论:建立的LC-MS/MS法准确可靠,富马酸替诺福韦二吡呋酯片两种制剂生物等效。Objective ： To establish a LC-MS/MS method for the determination of tenofovir in human plasma and study the pharmacokinetics and bioequivalence of tenofovir disoproxil fumarate tablets. Methods： In a randomized two-way crossover study,20 healthy male volunteers were divided into two groups, and were administered re- spectively with a single oral dose of test and reference preparations containing 300 mg of tenofovir disoproxil fumar- ate after an over-night fast. The blood samples were collected at predetermined time intervals up to 72 hours. The plasma concentration of tenofovir was determined by LC-MS/MS. The pharmacokinetic parameters were estimated by DAS 2.1.1. Results：The established LC-MS/MS method had linear calibration range over 2 - 1 200 ng·mL^-1 with a LLOQ of 2 ng·mL^-1 for tenofovir in human plasma. The intraand inter-batch standard deviations were less than 15%. The pharmacokinetic parameters for the test and reference tablets were as follows：Tmax both （0.5±0. 2） h, Cmax（604±207 ） and （573±189 ） ng·mL^-1, t1/2 （ 17. 1±2.9 ） and （ 17.4± 4.0 ） h, AUC0-72h （ 2 490±604 ） and （2 297±499 ） h·ng·mL^-1, respectively. Conclusion ： The method is suitable for the pharmacokinetic study of teno-fovir disoproxil fumarate tablets. The two preparations are bioequivalent.

关 键 词：替诺福韦二吡呋酯 药动学 生物等效性 液相色谱-串联质谱法 

分 类 号：R969.1[医药卫生—药理学] R978.7[医药卫生—药学]