泛昔洛韦缓释胶囊的人体药代动力学研究及其特征分析

Pharmacokinetics profile of famciclovir sustained release capsules in healthy volunteers

目的:研究泛昔洛韦缓释胶囊的人体药代动力学行为,证明受试制剂的缓释特征,评价其与参比制剂泛昔洛韦片的相对生物利用度。方法:单次给药试验四阶拉丁方试验设计,受试制剂250、375、750mg三剂量组及参比制剂750mg组;多次给药试验两周期随机交叉试验设计。HPLC法测定血药浓度,3P97软件进行数据处理及药代动力学分析。结果:12例受试者单次口服泛昔洛韦缓释胶囊250、375、750mg后,Cmax分别为(0.31±0.06)、(0.51±0.09)、(1.0±0.16)μg/mL,tmax分别为(4.4±1.8)、(4.0±1.4)、(4.3±1.8)h,平均滞留时间(MRT)分别为(6.9±1.3)、(7.3±1.0)、(7.6±0.7)h,AUC0-24分别为(3.3±0.8)、(5.2±1.1)、(11.3±1.4)μg·mL-1·h;普通片750mg给药后,Cmax为(3.81±0.38)μg/mL,tmax为(1.2±0.6)h,MRT为(3.3±0.4)h,AUC0-24为(13.7±1.5)μg·mL-1·h。缓释胶囊单次给药后的相对生物利用度为(81.96±2.54)%,两种制剂的生物利用度相当。10例受试者每日口服750 mg泛昔洛韦缓释胶囊和普通片3 d后缓释胶囊和普通片血药浓度均已达稳态,Cmin分别为(0.32±0.13)、(0.16±0.04)μg/mL。达稳态后的Cmax分别为(0.71±0.14)、(1.67±0.44)μg/mL,Cav分别为(0.44±0.09)、(0.56±0.13)μg/mL,波动度DF分别为(90±26)%、(270±59)%。缓释胶囊谷浓度明显高于普通片,波动度则明显小于普通片。结论:泛昔洛韦缓释胶囊具有明显缓释特征,并与普通片生物利用度相当。

AIM： To investigate the pharmacokinetic profile and relative bioavailability of Famciclovir sustained release capsules in healthy volunteers.METHODS： 12 healthy volunteers were divided into four group with single oral dose test famciclovir sustained release capsules（250,375,750 mg） and conventional Facmciclovir tablets（750 mg）according to an open randomized four way crossover design.A multi-dose test were given to 10 healthy volunteers according to an open randomized two way crossover design.The concentration of penciclovir in plasma after administration were determinded by HPLC.Pharmacokinetic parameters were calculated with 3P97 program.RESULTS： Concentration-time curves of penciclovir fitted to one-compartment mode,Cmax were（0.31±0.06）,（0.51±0.09）,（1.0±0.16） μg/mL,tmax（4.4±1.8）,（4.0±1.4）,（4.3±1.8） h,MRT（6.9±1.3）,（7.3±1.0）,（7.6±0.7） h,AUC0～24（3.3±0.8）,（5.2±1.1）,（11.3±1.4） μg·mL-1·h respectively for famciclovir sustained release capsules;Cmax were（3.81±0.38） μg/mL,tmax（1.2±0.6） h,MRT（3.3±0.4） h,AUC0-24（13.7±1.5） μg·mL-1·h for conventional tablet.The relative bioavailability was 81.96%±2.54%.The parameters after multi-doses of the sustain released capsules and conventional tablets were as follows： Cmin（0.32±0.13） and（0.16±0.04） μg/mL,Cmax（0.71±0.14） and 1.67±0.44 μg/mL,Cav（0.44±0.09） and（0.56±0.13） μg/mL,DF 90%±26% and 270%±59%,respectively.CONCLUSION： The sustain released capsules have the obvious sustained release characteristic.The two formulation of Famciclovir are of bioequivalence.