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Abstract #13945 Published in IGR 8-2
The pharmacokinetics of FK506 and its nanoparticles in aqueous humor of rabbits
Fei WL; Chen JQ; Zhong SL; Liu YM; Pang ZQ; Wang Z; Yuan J; Ye CTChinese Journal of Ophthalmology 2006; 42: 305-308
OBJECTIVE: To investigate the pharmacokinetics of FK506 and its nanoparticles in aqueous humor of rabbits applied with eye drops or subconjunctiva injections. METHODS: Forty-two New Zealand albino rabbits were divided into two groups. (1) Nanoparticle solution containing 10 μg FK506 was injected into the subconjunctiva or dropped on the conjunctival sac of the rabbits (68 eyes in 34 cases). (2) Eye drops containing 20 or 40 μg FK506 without nanoparticles were dropped on the conjunctival sac of the 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 the aqueous humor could be kept up to 16 h in the eye drops group. The range of FK506 concentration was between (15.50 ± 3.39) - (2.59 ± 0.83) ng/ml. FK506 in the aqueous humor can be maintained for 96 h by injecting into the subconjunctiva and the FK506 concentration was between (9.62 ± 2.19) - (2.60 ± 0.21) ng/ml from 6 - 96 h. Tmax and Cmax in eye drops were (1.25 ± 0.50) h and (15.52 ± 2.37) ng/ml respectively; while Tmax and Cmax in subconjunctiva injection were (64.00 ± 13.86) h and (10.16 ± 1.37) ng/ml respectively. Each AUC0→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 the conjunctival sac of the rabbits, all effective FK506 concentrations in the aqueous humor could not be kept over 4 h. Tmax was 1 h and Cmax was (18.93 ± 6.95) ng/ml in 20 μg FK506, while in 40 μg FK506 Tmax was 2h and Cmax was (28.33 ± 1.31) ng/ml. CONCLUSION: A solution with FK506 nanoparticle dropping onto the eye or injecting into the subconjunctiva could be sustained in rabbit aqueous humor for a longer time than a non-nanoparticle FK506 solution, while with injecting of nanoparticle FK506 solution it could be detected with a relatively low but longer effective concentration. LA: Chinese
Dr. W.L. Fei, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China
Classification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
