微透析-高效液相色谱法联用研究吴茱萸提取物的经皮吸收药动学特性

Characteristics of percutaneous absorption of evodia rutaecarpa extract characterized by cutaneous microdialysis-HPLC

目的:利用在体皮肤微透析技术研究吴茱萸提取物经皮吸收的特性。方法:以裸鼠为研究对象,建立在体经皮微透析采样技术,以吴茱萸碱和吴茱萸次碱为指标成分,采用高效液相色谱测定吴茱萸提取物经皮给药后透析液中的药物浓度,通过相对损失率的校正,计算皮肤药物浓度,并利用Kinetica 5.0软件对皮肤药物浓度和时间进行非房室模型拟合,计算相关统计参数。结果:吴茱萸提取物中吴茱萸碱的达峰时间为(150±15.3)min,半衰期(t1/2)(263.7±41.6)min;吴茱萸次碱的达峰时间为(90±2.1)min,半衰期(t1/2)(194±17.3)min;二者均能较快地达到峰值,并在较长的时间内保持稳定释放,使皮下组织中的药物浓度保持在一个相对恒定的水平。结论:本研究中所建立的微透析方法可用于吴茱萸提取物的皮肤药动学研究,吴茱萸碱和吴茱萸次碱可透过皮肤吸收而发挥临床药效。

OBJECTIVE To develop a cutaneous microdialysis to study the characteristics of percutaneous absorption of evodia rutaecarpa extract. METHODS By using nude mice, we developed the sampling technology of cutaneous microdialysis. Evodiamine （EVO） and rutaecarpine （RUT） were used the indes, HPLC method was used to determine the drug concentrations in dialysate after percutaneous absorption of evodia rutaecarpa extract, non compartment model fitting was performed for cutanoeus drug concentration and time by using Kinetica 5.0, to calculate relevant statistical moment parameters. RESULTS The time to peak （tmax） of EVO was （150 ± 15.3） min and its half time （t1/2） （263. 7 ± 41. 6）min; tmax of RUT was （90 ± 2. 1）min and its t1/2 was （194 ± 17. 3） min. Both extracts could reach the peak concentration quickly and release steadily in a relatively long period, to maintain a relatively constant drug concentration in subcutaneous tissues. CONCLUSION The microdialysis method in this study can be applied to investigate the cutaneous pharmacokinetics of evodia rutaecarpa extract. And EVO and RUT can exert clinical effects by percutaneous absorption.