更昔洛韦在犬体内血药浓度的测定及其分散片的相对生物利用度研究  

Determination of Serum Concentration of Ganciclovir in Dogs and Study on Relative Bioavailability of Ganciclovir Dispersible Tablets

作　　者：吴畏[1] 孟德胜[1] 

机构地区：[1]第三军医大学第三附属医院野战外科研究所药剂科,重庆市400042

出　　处：《中国药房》2010年第5期420-422,共3页China Pharmacy

摘　　要：目的:建立犬血清中更昔洛韦浓度测定的高效液相色谱法,并对更昔洛韦分散片进行药动学及相对生物利用度研究。方法:色谱柱为Dikma DiamonsilTM C18,流动相为0.015mol·mL-1磷酸二氢钾缓冲液(pH2.50,含乙腈0.25%),流速为1.75mL·min-1,检测波长为254nm,柱温为40℃。采用随机自身交叉对照试验设计,6只家犬分别单剂量口服更昔洛韦分散片与更昔洛韦胶囊后,采用高效液相色谱法测定血药浓度,DASver1.0软件处理药动学数据。结果:血清样品中更昔洛韦检测浓度在0.05025～100.5μg·mL-1范围内线性关系良好,方法回收率>90%,RSD<4%;分散片和胶囊的Cmax分别为(50.91±13.36)、(42.27±14.69)μg·mL-1,tmax分别为(2.70±0.67)、(3.20±0.57)h,AUC0～24分别为(361.50±72.76)、(280.60±101.87)μg·h·mL-1。分散片的相对生物利用度为128.83%。结论:所建立的更昔洛韦血药浓度测定方法灵敏度高,专一性强,能够满足药动学研究的要求。分散片与胶囊之间吸收速度等效,吸收程度不等效。OBJECTIVE ： To establish an HPLC method for determination of ganciclovir in serum of dogs and to study pharmacokinetics and relative bioavailability of Ganciclovir dispersible tablets. METHODS： The determination was performed on Dikma DiamonsilTM C18 column. The mobile phase consisted of 0.015 mol·mL^-1 monobasic potassium phosphate buffer solution （pH 2.50, containing 0.25% acetonitrile） with flow rate of 1.75 mL·min^-1 at detection wavelength of 254 nm. The column temperature was set at 40 ℃. In a randomized cross-over study, a single dose of dispersible tablets and the capsule were given to 6 dogs. An HPLC method was used to determine plasma concentration of ganciclovir in dogs and the pharmacokinetic data were treated by DASverl.0 software. RESULTS： The linear range of ganciclovir were 0.050 25-100.5 μg·mL^-1; the methodological recovery was larger than 90% （RSD〈4%）. The pharmacokinetics parameters of Ganciclovir dispersible tablets and Ganciclovir capsules were as follows： Cmax： （50.91±13.36） μg·mL^-1 vs. （42.27±14.69） μg·mL^-1; tmax： （2.70±0.67） h vs. （3.20±0.57） h; AUC0-24： （361.50±72.76） μg·h·mL^-1 vs. （280.60±101.87） μg·h·mL^-1. The relative bioavailability of Ganciclovir dispersible tablets was 128.83%. CONCLUSION： The established method is sensitive, specific and can be used for the pharmacokinetic studies. The dispersible tablet was bioequivalent to the capsule in absorption speed but not in absorption rate.

关 键 词：高效液相色谱法 更昔洛韦 犬 分散片 胶囊 血药浓度 药动学 相对生物利用度 

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