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


METHODS
63 dogs.


METHODS
Dogs received a single dose of marbofloxacin (2 mg x 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 x kg(-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 microg x mL(-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 marbofloxacin (2 mg x 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 x kg(-1) would be predicted to inhibit growth of Pseudomonas aeruginosa and all strains of staphylococci but would not eradicate streptococcal infections.


CONCLUSIONS
Marbofloxacin administered IV can penetrate the aqueous humor of canine eyes and may be suitable for prophylaxis or treatment of certain anterior chamber infections.
Regnier
Alain
A
Unité Associée INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, 31076 Toulouse, France.
Concordet
Didier
D
Schneider
Marc
M
Boisramé
Bernard
B
Toutain
Pierre-Louis
PL
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001082:Aqueous Humor / Q000378:metabolism*; D004283:Dog Diseases / Q000188:drug therapy / Q000517:prevention & control; D004285:Dogs; D005128:Eye Diseases / Q000188:drug therapy / Q000517:prevention & control / Q000662:veterinary; D005260:Female; D024841:Fluoroquinolones; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D015363:Quinolones / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C080260:marbofloxacin