盐酸川芎嗪透皮贴剂药代动力学研究

Pharmacokinetic study on transdermal patch with tramethylpyrazine hydrochloride

目的建立SD大鼠盐酸川芎嗪(TMPH)贴剂和灌胃给药后体内血药浓度的测定方法,计算贴剂组和灌胃组的药代动力学参数并进行比较。方法贴剂组:自制贴剂,SD大鼠背部给药(1.04 g/kg),分别于给药后0.5、1.5、3、4、5、6、7、8、9、12、17、24 h从尾部静脉取血;灌胃组:SD大鼠灌胃给药(1.6 mg/kg),分别在给药后5、8、10、13、15、21、34、45、61 min从尾部静脉取血;用HPLC测定两组大鼠体内TMPH的血药浓度,用DAS软件计算。结果灌胃组药代动力学参数:Tmax=0.167 h,Cmax=1.97 mg/L,T1/2=0.076 h,Auc0-t=0.597[(μg.h)/ml],Auc0-∞=0.650[(μg.h)/ml];贴剂组药代动力学参数:Tmax=5.917 h,Cmax=253 mg/L,T1/2=5.95 h,Auc0-t=3547.56[(μg.h)/ml],Auc0-∞=4132.47[(μg.h)/ml]。结论 TMPH灌胃给药时,达峰时间和半衰期都很短,说明TMPH普通制剂在体内吸收代谢非常迅速,难以长时间维持有效血药浓度;TMPH贴剂给药的达峰时间和半衰期大大延长,能够在较长时间内维持较高的血药浓度。

Objective To establish an assay method to detect the blood drug level in SD rats after receiving transdermal patch and intragastric administration with tramethylpyrazine hydrochloride（TMPH）,and to calculate pharmacokinetic parameters in the transdermal patch（TP）group and the intragastric administration（IA）group and make comparison between the two groups.Methods In the TP group,SD rats received the self-made transdermal patch on their backs（1.04 g/kg）.In 0.5,1.5,3,4,5,6,7,8,9,12,17 and 24 h after the administration respectively,their tail vein blood samples were obtained.In the IA group,SD rats received the intragastric administration（1.6 mg/kg）.In 5,8,10,13,15,21,34,45 and 61 min after the administration respectively,their tail vein blood samples were obtained.The blood drug levels of TMPH in these animals were detected by HPLC and calculated by DAS software.Results The pharmacokinetic parameters of TMPH in IA group were Tmax=0.167 h,Cmax=1.97 mg/L,T1/2=0.076 h,Auc0-t=0.597 [（μg·h）/ml],Auc0-∞=0.650 [（μg·h）/ml].Those were Tmax=5.917 h,Cmax=253 mg/L,T1/2=5.95 h,Auc0-t=3547.56 [（μg·h）/ml],Auc0-∞=4132.47 [（μg·h）/ml] in TP group,respectively.Conclusion The Tmax and T1/2 are very short when SD rats received the intragastic administration with TMPH,which shows the absorption and metabolism of TMPH in vivo is so fast that the effective blood drug level cannot be maintained for a long time.The Tmax and T1/2 of transdermal patch with TMPH are largely prolonged,which shows this administration can maintain a high blood drug level for a long time.