新型免疫抑制剂J2纳米混悬液结膜下注射后在兔外周血及眼内的分布  

Distribution of a novel immunosuppressant J2 nano-suspension in peripheral blood and eyes in rabbits after subconjunctival injection

作　　者：郭惠玲[1,2] 杜改萍[1] 胡莲娜[2] 王大江[1] 王丽强[1] 黄一飞[1] 

机构地区：[1]解放军总医院眼科,北京100853 [2]解放军306医院眼科,北京100101

出　　处：《第三军医大学学报》2013年第12期1225-1228,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30973245);全国博士后科学基金面上项目(20100481481)~~

摘　　要：目的观察新型免疫抑制剂J2-NS兔结膜下注射后在外周血及眼内组织的分布。方法 8～12周龄健康成年新西兰白兔18只(36眼),结膜下注射J2-NS,分别于注药后1、3 d,1、2、3、4周后取角膜、房水、虹膜以及外周血,HPLC法检测组织内的药物浓度(n=6),并使用WinNonlin药代动力学软件计算主要的药代动力学参数。结果 J2-NS兔结膜下注射后,观察期内在组织中均可检测到药物浓度。1 d到4周内血清药物浓度为(11.19±0.33)～(13.23±0.84)ng/mL;眼部组织中角膜的药物浓度最高,而在房水和虹膜内的药物浓度较低。在角膜内,1 d到4周内药物浓度为(5.72±1.67)～(11.86±4.35)ng/mg,峰浓度(Cmax)为11.861 3 ng/mg,达峰时间(Tmax)为1 d,曲线下面积(AUC)为201.561 5 ng/(mg.d),半衰期(T1/2)达45 d。结论新型免疫抑制剂J2-NS在结膜下单次注射后药物主要分布于外周血及角膜内,且在长时间能够维持有效药物浓度。Objective To investigate the distribution of a novel immunosuppressant, J2 nano-suspen- sion （NS）, in the peripheral blood and intraocular tissues in rabbits after subconjunctival injection. Methods Totally 18 healthy New Zealand white rabbits （36 eyes） , 8- to 12-week-old, were given an subeonjunctival injection of 0.2 ml 1% J2-NS. Drug concentration in the cornea, aqueous humor, and iris （6 eyes in each time point） and peripheral blood was detected by high-performance liquid chromatography （HPLC） on the days 1 and 3, and the weeks of 1, 2, 3 and 4 respectively after injection. The main pharmacokinetic parameters were calculated by pharmacokinetic software, WinNonlin. Results J2-NS at different concentrations was found in all detected organs during the observation period after injection. The serum concentration of J2-NS was 11.19 ±0.33 to 13.23 ±0.84 ng/mL from the day 1 to week 4 after injection. The cornea had the highest dose in all the eye tissues, but it was at lower dose in the aqueous humor and iris. The concentration was 5.72 ± 1.67 to 11.86 ±4.35 ng/mg in the cornea from the day 1 to week 4 after injection, with Cmax of 11. 861 3 ng/mg, Tmax of 1 d, and area under curve （AUC） of 201. 561 5 ng/（mg · d）and TI/2 of 45 d. Gonclusion Single subconjunctival injection of J2-NS leads the drug mainly being distributed in the peripheral blood and cornea, and being maintained at the effective drug concentration for a long time.

关 键 词：J2 纳米混悬液 药代动力学 

分 类 号：R322.91[医药卫生—人体解剖和组织胚胎学] R969.1[医药卫生—基础医学]