西罗莫司滴眼液在兔眼房水内的药动学

Pharmacokinetics of sirolimus in ocular aqueous humors of rabbit

目的探讨西罗莫司滴眼液单次滴兔眼后在房水中的药动学特征。方法 40只新西兰大白兔,局部滴入西罗莫司滴眼液50μL,采用高效液相色谱法测定兔眼房水中西罗莫司的药物浓度,用DAS1.0软件计算药动学参数。结果给药后0～120 h,西罗莫司在兔眼房水中的ρ_(max)为(84.92±37.04)μg·mL^(-1)(-1),t_(1/2)为(43.28±18.11)h,AUC_(0-6)为(1 747.44±571.36)μg·h·mL^(-1),AUC_(0-∞)为(2 335.25±702.42)μg·h·mL^(-1)。空白房水不干扰西罗莫司的含量测定。结论单次滴眼后西罗莫司可以快速穿透眼组织到达前房,并在房水中达到较高的药物浓度。

AIM To study pharmacokinetics of sirolimus in ocular aqueous humors of rabbit after ocular instillation. METHODS Forty New England rabbits were topically applied sirolimus eye drops 50 μL. Ocular aqueous humors were sampled at different intervals after drug instillation, and the drug levels were assayed by HPLC. The pharmacokinetics parameters were analyzed with DAS 1.0 software. RESULTS The peak concen- tration of sirolimus in aqueous humors was （84.92 ± 37.04） μg·mL-1, The half-lives of elimination was （43.28 ±18.11） h. The AUC0-6 was （1 747.44 ± 571.36） μg·h·mL^-1 and AUC0-∞ was （2 335.25 ±702.42）μg·h·mL^-1. Blank aqueous humors did not interfere with the determination of sirolimus. CONCLUSION Sirolimus could rapidly achieve a high concentration in aqueous humor after a single use of sirolimus eye drops in rabbit.