反相高效液相色谱法测定兔眼玻璃体内吲哚美辛浓度及药物动力学研究

Pharmacokinetics of indomethacin by intravitreous injection in rabbits

目的测定兔眼玻璃体内吲哚关辛（IN）浓度，研究其药物动力学特征并探讨给药方案。方法50只实验兔随机分为10组，每组5只10眼。除空白组外，其余各组每眼给予浓度为6mg·mL^-1IN溶液0．2mL，分别于注药后0．5、1、2、4、8、12、24、48、72h各处死1组兔子，取玻璃体样本，用反相高效液相色谱法（RP—HPLC）测定玻璃体腔内IN质量浓度。用DAS软件计算主要的药物动力学参数。结果吲哚美辛眼玻璃体内的消除半衰期为6．93h、药时曲线下面积为127．2μg·h^-1·mL^-1、清除率为0．04μg·h^-1结论兔眼玻璃体内吲哚美辛质量浓度变化符合一室模型，若按t1／2给药（τ=t1/2）则3～4次·d^-1的给药方案可达到稳态浓度（Css）。

Objective To study the pharmacokinetics of indomethacin by intravitreous injection and drug administration in rabbits. Methods Fifty rabbits were randomly divided into 10 groups （10 eyes of 5 rabbits each）. Indomethacin （0. 2 mL, 6 mg·mL^-1 ） was intravitreously injected in 45 rabbits, but was not administrated in the other 5 rabbits （a blank control group）. Rabbits of each group were killed after 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 h following the injection of indomethin and the vitreous specimens were obtained immediately. Indomethin concentrations were detected by reversed phase high performance liquid chromatography. The main parameters of pharmacokinetics were calculated through DAS pharmacokinetics software. Results The elimination half time （t1/2） of indometacin in the vitreous cavi- ty was 6.93 h, the drug-time area under curve （AUC） was 127.2μg·h^-1·mL^-1, and clearance was 0.04 μg·h^-1 . Conclusion The concentration-time curve of indomethacin in the vitreous cavity fits the one-compartment pharmacokinetic model. Css is attained by indomethacin vitreous injection 3-4 times per day.