治咳川贝枇杷滴丸中薄荷脑大鼠体内药物动力学及体内外相关性研究

Study on pharmacokinetics and in vitro/in vivo correlation of menthol in Zhike Chuanbei Pipa dropping pills in rats

该研究采用气相色谱(GC)法测定大鼠单剂量给药治咳川贝枇杷滴丸(ZCPDP)及不同剂量薄荷脑药材后血浆中薄荷脑的浓度,通过DAS 3.1.6软件计算药动学参数;采用Loo-Riegelman法计算体内累积吸收百分率,并与体外累积释放百分率进行线性回归,考察体内外相关性。结果显示ZCPDP中薄荷脑在大鼠体内药动学行为符合二房室模型特征,主要参数tmax为10 min,t1/2β为(183.93±52.75)min,CL/F为(0.426±0.194)L.min-1.kg-1,均与等剂量药材药动学参数无差异;不同剂量薄荷脑药材主要参数tmax,t1/2β,CL/F有显著差异(P<0.05),且AUC0-∞与给药剂量不成正比。ZCPDP累积吸收率对累积释放率回归方程为Fa=1.160 3Q-19.968(r=0.981 3)。实验结果表明ZCPDP中薄荷脑与等剂量薄荷脑药材在大鼠体内有相似的药动学行为,同时具有良好的体内外相关性;在19.2～570 mg.kg-1,薄荷脑在大鼠体内动力学过程存在显著性差异。

To determine the concentration of menthol in rat plasma by GC. Rats were administered with single dose of Zhike Chuanbei Pipa dropping pills （ZCPDP） and different doses of menthol herbs. DAS 3.1.6 software was used to calculate pharmacoki- netic parameters, and the accumulative absorption percentage of menthol was caletdated by Loo-Riegelman method. The linear regres- sion analysis was made in vitro/in vivo accumulative absorption percentages to detect the in vitro/in vivo correlation. The results of the study showed that the pharmacokinetics behavior of menthol in ZCPDP was in conformity with two-compartment model characteristics. The main parameters were： tmax was 10 min, t1/2β was （183. 93±52. 75） min, CL/F was （0. 426 ±0. 194） L · min-1 · kg^-1 , all of which were no difference between ZCPDP and menthol herbs with the same dosage. There were significant differences in tmax, t1/2β, CL/F between menthol herbs with different dosages （ P 〈 0. 05 ）, with indirect proportion between AUC0-∞ and dosage. The regression equation of ZCPDP＇s accumulative absorption percentage and accumulative release percentage was Fa = 1. 160 3Q - 19. 968, r = 0. 981 3. These results suggested that the pharmacokinetics behavior was similar between ZCPDP and menthol herbs with the same dos- age in rats, with good in vitro/in vivo correlation. There were significant differences in pharmacokinetics of menthol in the range of 19. 2-570 mg · kg^-1.