Fei Wen-lei, Chen Jia-qi, Zhong Shi-long, Liu Yong-min, Pang Zhi-qing, Wang Zheng, Yuan Jin, Ye Cheng-tian
Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Zhonghua Yan Ke Za Zhi. 2006 Apr;42(4):305-8.
To investigate the pharmacokinetics of FK506 and its nanoparticles in aqueous humor of rabbits applied with eye drops or subconjunctiva injections.
42 New Zealand albino rabbits were divided into 2 groups. (1) Nanoparticle solution containing 10 microg FK506 was injected into subconjunctiva or dropped on conjunctival sac of rabbits (68 eyes in 34 cases). (2) Eye drops containing 20 or 40 microg 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.
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 microg or 40 microg 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 microg FK506, while in 40 microg FK506 T(max) was 2h and C(max) was (28.33 +/- 1.31) ng/ml.
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.
研究兔眼局部应用滴眼液或结膜下注射后，FK506及其纳米粒在房水中的药代动力学。
42只新西兰白兔分为2组。（1）将含10μg FK506的纳米粒溶液注入兔结膜下或滴入结膜囊（34例共68眼）。（2）将不含纳米粒、含20μg或40μg FK506的滴眼液滴入兔结膜囊（8例共16眼）。局部给药后于不同时间采集房水，采用ELISA法测定FK506浓度。用3p87软件计算FK506的眼内药代动力学参数。
纳米粒溶液滴眼液组房水中FK506有效浓度可维持16小时，FK506浓度范围为（15.50±3.39）-（2.59±0.83）ng/ml。结膜下注射纳米粒溶液可使房水中FK506维持96小时，6-96小时FK506浓度为（9.62±2.19）-（2.60±?0.21）ng/ml。滴眼液组T(max)和C(max)分别为（1.25±0.50）小时和（15.52±2.37）ng/ml；结膜下注射组T(max)和C(max)分别为（64.00±13.86）小时和（10.16±1.37）ng/ml。各AUC(0→t)分别为（152.44±16.74）ng·ml-1·h-1和（612.48±54.39）ng·ml-1·h-1；各Ka分别为3.790±0.730和0.040±0.004；各MRT分别为（8.20±1.28）小时和（58.53±5.42）小时。在兔结膜囊应用不含纳米粒、含20μg或40μg FK506的滴眼液时，房水中所有FK506有效浓度均不能维持4小时以上。20μg FK506组T(max)为1小时，C(max)为（18.93±6.95）ng/ml；40μg FK506组T(max)为2小时，C(max)为（28.33±1.31）ng/ml。
FK506纳米粒溶液滴眼或结膜下注射在兔房水中维持时间比非纳米粒FK506溶液长，结膜下注射纳米粒FK506溶液能检测到相对低但有效浓度维持时间长。
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