唐草片对依非韦伦在大鼠体内药动学的影响  

Effects of Tangcao Tablets on the Pharmacokinetics of Efavirenz in Rats

作　　者：张丽军[1,2] 姚亚敏[1] 贾小芳[1] 尹林[1] 刘晓茜[1] 沈银忠[1] 卢洪洲[1] 程能能[2] 

机构地区：[1]上海市公共卫生临床中心,上海201508 [2]复旦大学药学院,上海200032

出　　处：《中国药房》2015年第4期454-457,共4页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81271834);重大新药创制课题资助项目(No.2012ZX09303013);传染病专项课题资助项目(No.2012ZX10001-003)

摘　　要：目的：研究唐草片对依非韦伦（EFV）在大鼠体内药动学的影响。方法：采用液相色谱-串联质谱（LC-MS/MS）法。色谱柱为Eclipse XDB-C18,流动相为0.1%甲酸水溶液-甲醇（20∶80,V/V）,流速为0.5 ml/min,柱温为30℃,进样量为10μl;采用电喷雾电离（ESI）,用于定量分析的离子对依次为m/z 515.2→276.2（内标：替米沙坦）,m/z 316.0→243.9（EFV）。18只SD大鼠随机均分为3组,分别单独灌胃EFV（54 mg/kg,即EFV组）、同时灌胃EFV和唐草片（54 mg/kg＋864 mg/kg,即EFV-0T组）、灌胃EFV 60 min后灌胃唐草片（54 mg/kg＋864 mg/kg,即EFV-60T组）。于大鼠灌胃给药前与末次给药后0.25、0.5、1.0、2.0、3.0、4.0、6.0、9.0、12.0、24.0h于颈动脉取血,测定不同时间血药浓度,以DAS 2.0软件计算药动学参数。结果：EFV质量浓度在75.0~9 600.0 ng/ml范围内与其和内标物峰面积之比呈良好线性关系,精密度试验的RSD值均小于10%,准确度为92.1%~102.0%,提取回收率为88.6%~91.0%,稳定性试验的RSD均小于10%。与EFV组比较,EFV-0T组AUC0-∞、t1/2、MRT0-∞降低,CL/F提高,差异有统计学意义（P〈0.01或P〈0.05）;EFV-60T组各指标差异无统计学意义（P〉0.05）。各组大鼠tmax、cmax、V/F差异无统计学意义。结论：EFV与唐草片同时服用会降低EFV血药浓度;当两药合用时,须在服用EFV 60 min后服用唐草片。OBJECTIVE： To study the effects of Tangcao tablets on the pharmacokinetics of efavirenz （EFV） in rats. METH- ODS： Liquid chromatography-tandem mass spectrometry （LC-MS/MS） method was used with column of Eclipse XDB-C18, the mo- bile phase of 0.1% formic acid-methanol （20：80, V/V）, a flow rate of 0.5 ml/min, the column temperature of 30 ℃ and the injec- tion volume of 10 μl. Electrospray ionization （ESI） was adopted, quantitative analysis of ion pairs were m/z 515.2→276.2 （internal standard： telmisartan）, m/z 316.0→243.9 （EFV）. 18 SD rats were divided into 3 groups randomly and evenly. Rats were given EFV alone （54 mg/kg, the EFV group）, EFV combined with Tangcao tablets （54 mg/kg＋864 mg/kg, the EFV-0T group） and Tang- cao tablets after giving EFV 60 min （54 mg/kg＋864 mg/kg, the EFV-60T group）. Plasma concentration at different time were test- ed by carotid blood before intragastric administration and 0.25,0.5, 1.0,2.0,3.0,4.0,6.0,9.0, 12.0,24.0 h after the last administra- tion. DAS 2.0 software was used to calculate the pharmacokinetic parameters. RESULTS： EFV concentration within 75.0-9 600.0 ng/ml and the ratio of EFV to internal standard peak area showed a good linear relationship. The RSD of precision test were less than 10%, accuracy were 92.1%-102.0% and the extraction recovery were 88.6%-91.0%. The RSD of stability test were less than 10%. Compared with EFV group, the AUC0-∞, t1/2, MRT0-∞ reduced and CL/F increased in EFV-0T group. There was significant dif- ference （P〈0.01 or P〈0.05）. There were no significant differences in the indicators of EFV-60T group （P〉0.05）. tma,, V/F and Cmax had no significant difference among 3 groups. CONCLUSIONS ： The plasma concentration of EFV can be reduced when it was co-administrated with Tangcao tablets simultaneously. It is necessary to take Tangcao tablets 60 min after EFV when they were co-administrated.

关 键 词：唐草片 依非韦伦 药动学 液相色谱-串联质谱 大鼠 

分 类 号：R917[医药卫生—药物分析学]