曲安奈德离子导入在兔眼房水中的药代动力学研究初探

Pharmacokinetic of triamcinolone acetonide iontophoresis in rabbit aqueous humor

目的研究曲安奈德（TA）离子导入在兔眼房水中的药代动力学特点,为临床用药提供实验依据。方法以成年新西兰兔为实验动物,TA离子导入兔眼,不同时间点抽取兔眼房水,采用高效液相色谱（HPLC）法测定样本中的药物浓度,用DAS1.0拟合计算药代动力学参数。结果线性范围为0.025～2.000μg/ml,药代动力学参数：t1/2为（2.6±0.4）h,AUC（0~24h）为（1.37±0.16）mg.L-1.h-1,AUC（0-∞）为（1.37±0.21）mg.L-1.h,Cmax为（0.66±0.15）mg/L,Tmax为（0.50±0.17）h。结论建立的房水中TAHPLC测定方法简便、准确、稳定、可靠,适用于TA的药代动力学研究,TA经离子导入吸收快,在房水中药物浓度较高,离子导入比眼球内注射安全性高,为临床改变给药途径提供药代动力学参数。

Objective To investigate the pharmacokinetic parameters of triamcinolone acetonide iontophoresis in rabbit aqueous humor and provide experimental evidence for clinical applications.Methods Healthy rabbits were iontophorezed triamcinolone acetonide into eyes and then aqueous humor was extracted at different time for analysis.The concentration of triamcinolone acetonide was determined by HPLC method.The pharmacokinetic parameters were calculated by DAS 1.0 program.Results The linear range was 0.025～2.000 g/ml.The other pharmacokinetic parameters as follows：t1/2 was（2.6±0.4） h,AUC（0~24h） was（1.37±0.16） mg.L-1.h,AUC（0-∞） was（1.37±0.21） mg.L-1.h,Cmax was（0.66± 0.15） mg/L,Tmax was（0.50±0.17） h.Conclusion The HPLC method for measurement of triamcinolone acetonide in aqueous humor appeared accurate,stable and reliable,and can be used in pharmacokinetics research on triamcinolone acetonide.Iontophoresis may lead to quicker absorption and persistent high drug level of triamcinolone acetonide,and also a safe profile when compared with intraocular injection.The present study provides pharmacokinetic parameters for another route of drug administration.