Intravitreal injection of methotrexate in an experimental rabbit model: Determination of pharmacokinetics

PURPOSE: To investigate the pharmacokinetics of intravitreally administered methotrexate. MATERIALS AND METHODS: Twenty-one New Zealand white rabbits were used in the study. The pharmacokinetics of intravitreally injected 800 μg/0.1 ml of methotrexate was investigated. Intravitreal concentration of the drug was measured at seven different times, in six eyes at each occasion, on a total of 42 eyes of 21 rabbits from a period of 30 minutes to 72 hours. RESULTS: The volume of distribution was calculated as 1.33 ml following intravitreal injection of 800 μg methotrexate. Vitreous concentrations of the drug were found to be decreasing related to the specific mathematical equation; drug concentration= 1426.73 e(-0.1182(time)) and remained over effective dose by 81 hours with a half life of 5.9 hours. CONCLUSIONS: These findings evidenced those vitreous levels of methotrexate at various time intervals after 800 μg intravitreal injections which formulated a mathematical equation for calculation of vitreous level of the drug at each hour.