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Ocular pharmacokinetics and bioavailability of 0.2% ganciclovir in-situ gelling eye drops


, : Ocular pharmacokinetics and bioavailability of 0.2% ganciclovir in-situ gelling eye drops. Chinese Journal of Ophthalmology 42(7): 637-641

To compared the pharmacokinetics and bioavailability of 0.2% ganciclovir (GCV) in-situ gelling eye drops (GCV-ISG) with common GCV eye drops (GCV-ED) in rabbits. Forty-eight healthy albino rabbits were randomly divided into 2 groups, each group included 24 rabbits and 3 rabbits (6 eyes) were used at each time points. Each eye received 50 microl of GCV-ISG in experimental group, and the same amount of GCV-ED was given in the other group as the control. The tears and aqueous humors were collected at 5, 10, 15, 30, 45, 60, 90 and 120 minutes following topical application of GCV-ISG and GCV-ED, respectively, and the corneas were immediately dissected after euthanized. The samples from 6 eyes (3 animals) were obtained at each designed time point. All samples were stored -60 degrees C and then were assayed by reversed phase high performance liquid chromatography (HPLC). An unpaired Student's t-test and 3p97 pharmacokinetics software were used as statistical analysis. The drug levels in tears corneas and aqueous were significantly higher for GCV-ISG group than GCV-ED group at 5, 10 minutes (P < 0.05) and 120 minutes (P < 0.01). The areas under the curve (AUC0-120) of the drug concentrations versus times in tears, corneas and aqueous humors for GCV-ISG group were 2.22, 5.47 and 3.40 times as high as GCV-ED group within designed duration, respectively. The peak concentrations of GCV in aqueous humors for GCV-ISG group and the GCV-ED group were 4.79 microg/ml and 0.96 microg/ml, respectively. The half-lives of GCV in aqueous humors and corneas for GCV-ISG group were 59 minutes and 223 minutes, and for GCV-ED group were 43 minutes and 87 minutes, respectively. The peak concentration of GCV in aqueous humor in GCV-ISG group was 4.99 times higher than that in GCV-ED group (P < 0.01). 0.2% ganciclovir in-situ gelling eye drops significantly increases the drug penetration into cornea and aqueous humor, and prolongs the residence time in cornea and aqueous humor. The results suggest that 0.2% ganciclovir in-situ gelling eye drops may enhance the ocular bioavailability of ganciclovir in rabbit eye.

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PMID: 17081425


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