Population pharmacokinetics of marbofloxacin in aqueous humor after intravenous administration in dogs.

Objective—To evaluate, by use of population phar- macokinetics, the disposition of marbofloxacin in the aqueous humor after IV administration in dogs and identify its potential usefulness in the prophylaxis and treatment of intraocular infection. Animals—63 dogs. Methods—Dogs received a single dose of mar- bofloxacin (2 mgkg -1 , IV) at various time intervals before cataract surgery. Aqueous humor and blood samples were collected at the beginning of surgery. Marbofloxacin concentrations were measured by high-pressure liquid chromatography. Data were ana- lyzed with a nonlinear mixed-effect model and, by use of population pharmacokinetic parameters, the time course of aqueous humor concentration was simulat- ed for single doses of 3, 4, and 5.5 mgkg -1 IV. Pharmacodynamic surrogate markers and measured aqueous humor concentrations were used to predict in vivo antimicrobial activity. Results—A maximum marbofloxacin concentration of 0.41 ± 0.17 µgmL -1 was reached in the aqueous humor 3.5 hours after IV administration. In the post- distributive phase, marbofloxacin disappeared from aqueous humor with a half-life of 780 minutes. The percentage penetration into the aqueous humor was 38%. Predictors of antimicrobial effects of mar- bofloxacin (2 mgkg -1 , IV) indicated that growth of the enterobacteriaceae and certain staphylococcal species would be inhibited in the aqueous humor. Marbofloxacin administered IV at a dose of 5.5 mgkg -1 would be predicted to inhibit growth of Pseudomonas aeruginosa and all strains of staphylo- cocci but would not eradicate streptococcal infec- tions. Conclusions and Clinical Relevance—Marbo- floxacin administered IV can penetrate the aqueous humor of canine eyes and may be suitable for pro- phylaxis or treatment of certain anterior chamber infections. (Am J Vet Res 2003;64:889-893)