采用在体分时取样法研究2种咪喹莫特乳膏的裸鼠皮肤药动学行为

目的:采用裸鼠在体分时取样法比较国产和进口2种咪喹莫特乳膏的皮肤药动学行为。方法:分别在裸鼠相同面积的皮肤上涂抹2种乳膏各约0.03g(n=32)后,于0.25、0.5、1、2、4、6、8、24h取皮制备匀浆,采用高效液相色谱法测定皮肤中的药物浓度,比较2种制剂的药动学参数并计算偏差以对该方法进行评价。结果:国产和进口乳膏的咪喹莫特cmax分别为(82.80±8.13)、(76.46±13.08)μg·g-1,tmax分别为(6.0±0.0)、(5.0±1.2)h,t1/2分别为(25.28±4.27)、(23.30±7.42)h,AUC0～24h分别为(992.27±226.55)、(1037.02±175.93)μg·h·g-1,二者比较均无统计学差异(P>0.05)。2种制剂cmax、tmax、AUC0～24h的RSD分别为9.8%、17.1%,0、24.0%,22.8%、17.0%。结论:2种乳膏的裸鼠皮肤药动学行为无显著性差异;主要药动学参数的RSD偏差较小,表明在体给药分时取样法能较好地反映药物在裸鼠体内的经皮代谢过程,适用于临床前外用药物的皮肤药动学筛选与评价研究。

Dermatopharmacokinefic Study of 2 Kinds of Imiquimod Creams in Nude Mice by Using Time-share Sam- piing Method in Vivo

OBJECTIVE： To compare the dermatophannacokinetics of domestic and imported Imiquimod cream by time-share sampling method in vivo. METHODS： After administration of 2 kinds of Imiquimod cream 0.03 g on the same area of skin （n=32）, the nude mice were sacrificed at 0.25, 0.5, 1,2,4,6,8 or 24 h and the skin of the back was made into homogenate. The drug concentration in skin was determined by HPLC. The pharmakinetic parameters and deviation were calculated to evaluate the meth- od. RESULTS： Pharmacokinetic parameters of domestic cream vs. imported one were as follows： Cmax： （82.80 ± 8.13） vs.（76.46 ± 13.08） μg.g-1; tmax： （6.0 ± 0.0） vs.（5.0 ± 1.2） h; t1/2： （25.28 ± 4.27） vs.（23.30 ± 7.42） h; AUC0-24h： （992.27 ± 226.55） vs. （1 037.02 ± 175.93） μg.h.g-1, respectively. The RSD of Cmax, tmax and AUC0-24h were 9.8% and 17.1%, 0 and 24.0%, 22.8% and 17.0%, re- spectively. CONCLUSION： The pharmacokinetic parameters of 2 kinds of cream have no significant differences, which show that RSDs of pharmacokinetic parameters are small. The in vivo time-share sampling method can better reflect the dermatopharmacoki- netics of imiquimod in nude mice. It can be used for the evaluation and screening of the dermatopharmacokinetics of preclinical drugs for external use.