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

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  • 1 Unité Associée INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, 31076 Toulouse, France.
  • | 2 Unité Associée INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, 31076 Toulouse, France.
  • | 3 Laboratoire Vétoquinol, 70204 Lure, France.
  • | 4 Laboratoire Vétoquinol, 70204 Lure, France.
  • | 5 Unité Associée INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, 31076 Toulouse, France.

Abstract

Objective—To evaluate, by use of population pharmacokinetics, 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 marbofloxacin (2 mg · kg–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 analyzed with a nonlinear mixed-effect model and, by use of population pharmacokinetic parameters, the time course of aqueous humor concentration was simulated for single doses of 3, 4, and 5.5 mg · kg–1IV. 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 µg·mL–1 was reached in the aqueous humor 3.5 hours after IV administration. In the postdistributive 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 marbofloxacin (2 mg · kg–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 mg · kg–1 would be predicted to inhibit growth of Pseudomonas aeruginosa and all strains of staphylococci but would not eradicate streptococcal infections.

Conclusions and Clinical Relevance—Marbofloxacin administered IV can penetrate the aqueous humor of canine eyes and may be suitable for prophylaxis or treatment of certain anterior chamber infections. (Am J Vet Res 2003;64:889–893)

Abstract

Objective—To evaluate, by use of population pharmacokinetics, 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 marbofloxacin (2 mg · kg–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 analyzed with a nonlinear mixed-effect model and, by use of population pharmacokinetic parameters, the time course of aqueous humor concentration was simulated for single doses of 3, 4, and 5.5 mg · kg–1IV. 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 µg·mL–1 was reached in the aqueous humor 3.5 hours after IV administration. In the postdistributive 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 marbofloxacin (2 mg · kg–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 mg · kg–1 would be predicted to inhibit growth of Pseudomonas aeruginosa and all strains of staphylococci but would not eradicate streptococcal infections.

Conclusions and Clinical Relevance—Marbofloxacin administered IV can penetrate the aqueous humor of canine eyes and may be suitable for prophylaxis or treatment of certain anterior chamber infections. (Am J Vet Res 2003;64:889–893)