【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。更多还原

【Abstract】 OBJECTIVE:To study the effects of Tangcao tablets on the pharmacokinetics of efavirenz(EFV)in rats. METHODS:Liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was used with column of Eclipse XDB-C18,the mobile 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 injection 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 Tangcao tablets after giving EFV 60 min(54 mg/kg+864 mg/kg,the EFV-60 T group). Plasma concentration at different time were tested 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 administration. DAS 2.0 software was used to calculate the pharmacokinetic parameters. RESULTS:EFV concentration within 75.0-9 600.0ng/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 than10%. Compared with EFV group,the AUC0-∞,t1/2,MRT0-∞reduced and CL/F increased in EFV-0T group. There was significant difference(P<0.01 or P<0.05). There were no significant differences in the indicators of EFV-60 T group(P>0.05). tmax,V/F and cmaxhad 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.更多还原