Ocular pharmacokinetics and bioavailability of gatifloxacin ophthalmic gel in rabbits
AIM: To assay and compare the drug levels in tears, corneas and aqueous humors at different times after single and multiple topical application of 3 g/L gatifloxacin ophthalmic gel (GTX-Gel), 3 mL/L gatifloxacin ophthalmic solutions (GTX-ED) to rabbits, and evaluate the ocular bioavailability of GTX-Gel. METHODS: Single dose: Japanese white rabbits were randomly divided into 2 groups, each group including 40 rabbits. One of group received 50 mg of GTX-Gel, the other groups received 50 L of GTX-ED, respectively. The two eyes of each rabbit received the same dose of the medications. The aqueous humors were collected at prescheduled time points following topical application of GTX-Gel or GTX-ED, respectively, and the corneas were immediately dissected after euthanized. All samples were stored - 60℃. High performance liquid chromatography (HPLC) analysis was used as a detection method. Statistical tests used included an unpaired Student's t-test and 3p97 pharmacokinetics software. RESULTS: The drug levels in corneas at 5-360 min time points for GTX-Gel group were significantly higher than GTX-ED group at corresponding times(P ＜ 0.05). The area under the curve (AUC) of the drug concentrations vs times in corneas for GTX-Gel group was 4.8 times as high as GTX-ED group within designed duration. The drug levels in aqueous humors (AH) at 5-360 min for GTX-Gel group were significantly higher than GTX-ED group at corresponding times(P ＜ 0.05). The AUC in AH for GTX-Gel group was 5.5 times as high as GTX-ED group within designed duration. For the multiple dose, The drug levels in corneas for the GTX-Gel after 2,4 and 12 h last application were 5.3, 2.2 and 3.0 times as high as GTX-ED group at corresponding time points, respectively, and in aqueous humors for GTX-Gel group were 7.1, 2.7 and 1.5 times as high as GTX-ED as corresponding time points, respectively. CONCLUSION: Gatifloxacin ophthalmic gel significantly increased the drug levels in corneas and aqueous humors compared to the GTX ophthalmic solutions, thus increased the ocular bioavailability.
NETL
NSTL
万方数据
维普
