【摘要】 目的探讨FK506及其纳米粒的房水药代动力学特征。方法42只新西兰白兔分为:（1）FK506纳米胶体液滴眼组（18只兔）和注射组（16只兔）:双眼结膜囊滴入或结膜下注射10μgFK506的纳米胶体溶液;（2）不含纳米微粒的FK506滴眼组（8只兔）:再分为2个亚组,即双眼结膜囊分别滴入20μg和40μg FK506的滴眼液。不同时间点采集房水,酶联免疫法测定房水中FK506含量,计算药代动力学参数。结果含10μg FK506的纳米胶体溶液结膜下注射和滴眼后房水有效药物浓度可分别维持96 h和16 h;结膜下注射后2 h房水浓度为（1.15±0.25）ng/m、l6⁹6 h房水浓度为（9.62±2.19）^2.60±0.21ng/m l,滴眼16 h内房水浓度为（15.50±3.39）^2.59±0.83ng/m l;药代动力学参数分别为:达峰时间（Tm ax）（64.00±13.86）h和（1.25±0.50）h,达峰浓度（Cm ax）（10.16±1.37）ng/m l和（15.52±2.37）ng/m l,曲线下面积（AUC0→t）（612.48±54.39）ng.m l-1.h-1和（152.44±16.74）ng.m l-1.h-1,吸收速率常数（Ka）0.040±0.004和3.790±0.730,平均滞留时间（MRT）（58.53±5.42）h和（8.20±1.28）h。房水中FK506质量浓度呈一室模型。不含纳米微粒的FK506（20μg和40μg）液滴眼后房水有效药物浓度维持均≤4 h;其中含20μgFK506液的Tm ax为1 h,Cm ax为（18.93±6.95）ng/m l;含40μg FK506液的Tm ax为2 h;Cm ax为（28.33±1.31）ng/m。l结论采用FK506纳米粒胶体溶液行结膜下注射和滴眼时均可延长FK506药物在房水中的滞留时间,而且结膜下注射能使房水中维持的有效药物浓度相对较低和时间更长更多还原

【Abstract】 Objective To investigate the pharmacokinetics of FK506 and its nanoparticles in aqueous humor of rabbits applied with eye drops or subconjunctiva injections.Methods 42 New Zealand albino rabbits were divided into 2 groups.（1）Nanoparticle solution containing 10 μg FK506 was injected into subconjunctiva or dropped on conjunctival sac of rabbits（68 eyes in 34 cases）.（2） Eye drops containing 20 or 40 μg FK506 without nanoparticles were dropped on conjunctival sac of rabbits（16 eyes in 8 cases）.Aqueous humor was collected at different times after local administration and FK506 concentrations were measured by ELISA.Ocular pharmacokinetic parameters of FK506 were calculated by 3p87 software.Results In the solution containing nanoparticle,the effective FK506 concentration in aqueous humor could be kept up to 16 h in eye drops group.The range of FK506 concentration was between（15.50±3.39）-（2.59±0.83） ng/ml.FK506 in aqueous humor can be maintained for 96 h by injecting into subconjunctiva and FK506 concentration were between（9.62±2.19）-（2.60±0.21） ng/ml from 6-96 h.T_max and C_max in eye drops were（1.25±0.50）h and（15.52±2.37） ng/ml respectively;while T_max and C_max in subconjunctiva injection were（64.00±13.86）h and（10.16±1.37） ng/ml respectively.Each AUC_0→t was（152.44±16.74） ng·ml^-1·h^-1 and（612.48±54.39） ng·ml^-1·h^-1 respectively;each Ka was 3.790±0.730 and 0.040±0.004 respectively;and each MRT was（8.20±1.28）h and（58.53±5.42）h respectively.In the eye drops containing 20 μg or 40 μg FK506 but without nanoparticles applied in conjunctival sac of rabbits,all effective FK506 concentrations in aqueous humor could not be kept over 4 h.T_max was 1 h and C_max was（18.93±6.95） ng/ml in 20 μg FK506,while in 40 μg FK506 T_max was 2h and C_max was（28.33±1.31）ng/ml.Conclusion Solution with FK506 nanoparticle dropping onto the eye or injecting into subconjunctiva could be sustained in rabbit aqueous humor for a longer time than non-nanoparticle FK506 solution,while with injecting of nanoparticle FK506 solution it could be detected with a relative low but longer effective concentration.更多还原