论文部分内容阅读
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 observe the distribution of the new immunosuppressant J2-NS in peripheral blood and intraocular tissues after subconjunctival injection. Methods Eighteen (36 eyes) healthy adult New Zealand white rabbits (8-12 weeks old) were injected subconjunctivally with J2-NS. The corneas, aqueous humor, Iris, and peripheral blood were assayed for the drug concentration in the tissue by HPLC (n = 6) and the main pharmacokinetic parameters were calculated using the WinNonlin pharmacokinetics software. Results After J2-NS subconjunctival injection, the drug concentration was detected in the tissues during the observation period. Serum drug concentration was (11.19 ± 0.33) ~ (13.23 ± 0.84) ng / mL in 1 d to 4 wk; corneal drug concentration was the highest in ocular tissues and lower in aqueous humor and iris. In the cornea, the drug concentration was (5.72 ± 1.67) ~ (11.86 ± 4.35) ng / mg within 1 d to 4 weeks, the peak concentration (Cmax) was 11.861 3 ng / mg and the peak time (Tmax) The area under the curve (AUC) was 201.561 5 ng / (mg.d) and the half-life (T1 / 2) was 45 d. Conclusion The new immunosuppressant J2-NS is mainly distributed in peripheral blood and cornea after single injection under the conjunctiva, and can maintain the effective drug concentration for a long time.