【作者】 李见春； 陈飞虎； 蒋志文；

【Author】 LI Jian-chun~(1,2),Chen fei-hu~1,JIANG Zhi-wen~2 1 Pharmacy College of Anhui Medical University,2 Department of pharmacy,Bengbu Medical College, Anhui Bengbu 233030

【机构】 安徽医科大学药学院； 蚌埠医学院药学系；

【摘要】 目的:研究盐酸环苯扎林片在健康人体单、多次给药的药代动力学。方法:40名健康志愿者,随机平均分为4组（男女各半）,单次给药分别口服盐酸环苯扎林片5 mg、10 mg、15 mg,多次给药10 mg,q8h×6 d。按试验方案采血,高效液相色谱-质谱联用法测定血清中环苯扎林浓度,DAS2.0软件计算药代动力学参数。结果:健康受试者单次给药5 mg、10 mg、15 mg主要药代动力学参数分别为:t_max（5.1±2.8）、（5.3±1.9）和（4.0±1.8）h;C_max（5.0±2.0）、（7.2±3.2）和（17.2±8.8）μg·L^-1;t_1/2β（33.7±15.8）、（31.0±7.4）和（33.8±11.5）h;AUC_0-t（138.9±28.0）、（250.0±133.9）和（405.2±159.3）μg·h·L^-1。多剂量给药10 mg达稳态时,主要药代动力学参数为t_max（3.0±1.3）;C_max（34.6±7.4）μg·L^-1;t_1/2β（38.2±12.7）h;AUC_0-t1418.0±584.7)μg·h·L^-1;C_min（23.3±6.5）μg·L^-1;AUC_SS（224.5±52.8）μg·h·L^-1;Cav（28.1±6.6）μg·L^-1;DF（0.41±0.29）。结论:盐酸环苯扎林片口服给药5～15 mg剂量范围内,体内过程呈线性;10 mg,q8h连续多次6天,血药浓度d 4已达稳态,体内出现较为明显蓄积;男女性别间体内过程未见显著性差别。更多还原

【Abstract】 Objective:To investigate the pharmacokinetics of cyclobenzaprine hydrochloride tablets with a single and multi-dose p.o.administration in Chinese healthy volunteers.Methods:40 healthy volunteers were randomly divided into four groups with 5 male and 5 females in each group.The volunteers in three groups were administrated with single dose of cyclobenzaprine hydrochloride tablets 5,10,15 mg. respectively.The last group was administrated with the dose of cyclobenzaprine hydrochloride tablets 10 mg,tid,till the sixth day.Blood samples were collected according to the protocol and serum concentration of cyclobenzaprine were measured by validated LC-MS/MS.DAS2.0 software was performed for calculating pharmacokinetic parameters.Results:The main pharmacokinetics parameters of cyclobenzaprine in volunteers who were administrated with a single dose of 5,10,15 mg were as follows: t_max（5.1±2.8）,（5.3±1.9） and（4.0±1.8） h;C_max（5.0±2.0）,（7.2±3.2） and（17.2±8.8）μg·L^-1;t_1/2β（33.7±15.8）, （31.0±7.4） and（33.8±11.5） h;AUC_0-t（138.9±28.0）,（250.0±133.9） and（405.2±159.3）μg·h·L^-1,respectively. The main pharmacokinetics parameters of cyclobenzaprine hydrochloride after multi-dose（10 mg） administration were as follows:t_max（3.0±1.3）,C_max（34.6±7.4）μg·L^-1,t₍1/2β0（38.2±12.7） h, AUC_0-t（1418.0±584.7）μg·h·L^-1,C_min（23.3±6.5）μg·L^-1,AUC_ss（224.5±52.8）μg·h·L^-1,Cav（28.1±6.6）μg·L^-1 and DF（0.41±0.29）.Conclusion:After administration of multi-dose cyclobenzaprine hydrochloride tablets （10 mg tid p.o.）,serum concentrations of cyclobenzaprine have been in steady state till fourth day and have obviously accumulation in vivo.Increase of cyclobenzaprine hydrochloride tablets dosage（5～15 mg） is positively calculated with increase of C_max and AUC_0-t and simultaneously with no significant difference of physiological disposition between the male and female.更多还原