单剂量口服阿德福韦酯片人体药动学研究

目的:研究单剂量口服阿德福韦酯片在健康人体中的药动学。方法:采用随机、开放、三交叉设计试验,12名健康志愿者随机分为3组,在3周期里单次空腹口服阿德福韦酯片5、10、30mg,用高效液相色谱-质谱串联法测定血浆药物浓度,计算药动学参数。结果:单剂量口服阿德福韦酯片5、10、30mg后阿德福韦的主要药动学参数Cmax分别为(11·4±3·7)、(25·4±8·2)、(76·3±23·0)ng·mL-1,tmax分别为(1·69±1·41)、(0·90±0·56)、(0·94±0·50)h,AUC0～t分别为(102·7±51·7)、(235·0±82·3)、(715·4±267·6)ng·h·mL-1,AUC0～∞分别为(168·7±30·7)、(266·2±83·7)、(741·5±273·9)ng·h·mL-1。结论:阿德福韦酯吸收迅速,Cmax、AUC与剂量呈正相关。健康志愿者单剂量口服阿德福韦酯片5～30mg较安全。

Pharmacokinetics of Single Oral Dose Adefovir Dipivoxil Tablet in Healthy Volunteer

OBJECTIVE:To study the pharmacokinetics of oral single dose adefovir dipivoxil(ADV) tablet in Chinese healthy volunteers.METHODS:The study was a randomized,open,three-way crossover study.Twelve healthy volunteers were randomly assigned to receive single oral dose of 5 mg(Group A),10mg(Group B) or 30 mg(Group C) ADV tablets in three weeks.The plasma concentrations of ADV were determined by LC/MS/MS method.The pharmacokinetic parameters were computed.RESULTS:The main pharmacokinetic parameters in Group A,B and C were as follows:Cmax were(11.4± 3.7),(25.4± 8.2) and(76.3± 23.0) ng· mL-1;tmax were(1.69± 1.41),(0.90± 0.56) and(0.94± 0.50) h;AUC0～ t were(102.7± 51.7),(235.0± 82.3) and(715.4± 267.6) ng· h.mL-1;AUC0～ ∞ were(168.7± 30.7),(266.2± 83.7) and(741.5± 273.9) ng· h· mL-1,respectively.CONCLUSION:ADV tablets had a rapid absorption in healthy volunteers and the Cmax and AUC of adefovir tablets were directly correlated to doses.It is safe for healthy volunteers to take ADV tablets at a dose of 5～30mg.