吲哚美辛玻璃体腔内注射的药代动力学研究

Pharmacokinety of intravitreous administration of indomethin

目的研究兔眼玻璃体腔内注射吲哚美辛(IN)后的药代动力学特点。方法40只新西兰大耳白兔随机分为10组,每组4只8眼。除空白组外,其余各组每眼给予吲哚美辛3mg,分别于注药后30min,1、2、4、8、12、24、48、72h各处死一组兔子,取玻璃体样本,用反向高效液相色谱法(RP-HPLC)测定玻璃体腔内IN质量浓度。用DAS软件计算主要的药代动力学参数。结果IN在玻璃体腔内消除半衰期(t1/2)为7.71h、药-时曲线下面积(AUC)为3785.59μg/(ml.h)、清除率(CL)为0.0015μg/h结论RP-HPLC测定玻璃体腔内IN质量浓度灵敏、特异、准确,IN在玻璃体内的t1/2为7.71h。

Objective Because of the recurrent nature of the disease, proliferative vitreoretinopathy （PVR） causes blindness in approximately 10% of patients undergoing retinal re-attachment surgery. Indomethin can prevent PVR, The present study examined the pharmacokinetics of indomethin after intravitreal injection in rabbits, Methods Forty New Zealand rabbits were randomly divided into 10 groups and 8 eyes of 4 animals for each. 3 mg of indomethin was intravitreously injected in 36 rabbits, and drug did not administrated in 4 rabbits of blank control group. Rabbits of each group were killed at 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours following injection of indomethin respectively and the vitreous specimens were obtained immediately. Indomethin concentrations were detected by reversed phase high performance liquid chromatography （RP-HPLC）. The main parameters of pharmacokinetics were calculated through DAS pharmacokinetics software. Results The half life for elimination （t1/2） of indomethin from vitreous was 7.71 hours. The area under concentration-time curve（AUC） was 3 785.59 μg/（ml·h）. The clearance （CL） was 0.001 5 μg/h. The mass concentration was （347.467±15.671） μg/ml, （305.951±6.608） μg/ml, （233.234±30.910） μg/ml, （228.503±22.080） μg/ml, （172.363±11.486） μg/ml, （113.259±11.738） μg/ml, （47.743±2.440） μg/ml, （17.457±1.385） μg/ml and （6.757±0.843） μg/ml at 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after injection of 30 mg/ml indomethin, respectively. Conclusion The half life for elimination of indomethin from vitreous is not long. Indomethin can reduce the toxicity of retina and may be a useful pharmacologic tool to control PVR.