溶菌酶滴眼液兔眼药代动力学研究

Pharmacokinetic study of lysozyme eye drops in rabbits

目的比较溶菌酶滴眼液兔眼单多次给药后泪液中溶菌酶的药代动力学特征,以及在正常和受损角膜的兔眼组织和血清分布情况。方法12只新西兰兔用于动力学研究,分别单多次给予溶菌酶滴眼液后不同时间点收集泪液。24只用于眼组织和体循环分布研究,单次给予溶菌酶滴眼液后不同时间点收集眼组织和血清。采用酶联免疫分析法测定不同组织中溶菌酶的浓度,Winnonlin软件计算药动学参数。结果与单次给药相比,多次给药后泪液中溶菌酶的含量显著增加,Cmax和AUC0-24h分别约是单次给药的3.3倍和6.1倍,且t1/2也延长到10.6 h。角膜上皮去除后,溶菌酶在角膜和房水分布均显著增多,在结膜分布未见显著变化。血清中均未检出溶菌酶的量。结论溶菌酶滴眼液以每天4次连续给药比单次给药在泪液的分布增加,作用时间延长。上皮受损后角膜对溶菌酶的屏障作用明显减弱,故角膜和房水中分布升高。

Purpose To investigate the pharmacokinetics of 0.5%lysozyme eye drops in tears with different dosing frequencies in rabbits,as well the ocular and serum distribution through both normal and deepithelialized cornea.Methods 12 rabbits were used for the pharmacokinetic study.Tears were collected at different time points after single and multiple administration.24 rabbits were used for the ocular tissue and systemic circulation distribution study.Serum specimens and ocular tissues were collected at different time points after single administration.The concentration of lysozyme in each specimen was determined by enzyme-linked immunosorbent assay,and the pharmacokinetic parameters were calculated by Winnonlin software.Results The Cmax and AUC0-24h after multiple dosing were more than 3.3 and 6.1 times higher than those of the single dosing.The t1/2 also increased to 10.6 h.After the removal of corneal epithelium,the amount of lysozyme in cornea and aqueous humor increased significantly.There was no significant difference in conjunctiva.Lysozyme levels were undetectable in serum at all time points in either group with normal or deepithelialized corneas.Conclusion:The distribution of lysozyme in tears increases with QID compared to single dose.Moreover,the half-life and the action time are prolonged.De-epithelialization of the cornea significantly weakens the barrier to lysozyme.The distribution of lysozyme significantly increases both in the cornea and aqueous humor.