Intraocular pharmacokinetics of intravenously administered marbofloxacin in rabbits with experimentally induced acute endophthalmitis.
OBJECTIVE
To compare penetration of IV administered marbofloxacin in intraocular fluids of healthy and inflamed eyes in rabbits with endotoxin-induced endophthalmitis.


METHODS
35 pigmented rabbits.


METHODS
Endophthalmitis was induced in the right eye via intravitreal administration of Escherichia coli endotoxin. The left eye was a control eye. After 24 hours, a single dose of marbofloxacin (4 mg/kg, IV) was administered. Groups of rabbits (n = 5/group) were euthanized 0.5, 1, 2, 4, 6, 10, and 18 hours later, and blood and ocular fluids were collected. Marbofloxacin concentrations were determined via reverse-phase high-performance liquid chromatography, and pharmacokinetic analysis of the data was performed with a mono-compartmental model.


RESULTS
Mean area under the aqueous concentration-time curve was significantly lower in control eyes (1.64 +/- 0.07 microg*h/mL) than in inflamed eyes (3.31 +/- 0.11 microg*h/mL). Similarly, drug penetration into aqueous humor was 33% and 65% for control eyes and inflamed eyes, respectively. Mean area under the vitreous humor concentration-time curve for control eyes(1.75 +/- 0.05 microg*h/mL) was significantly less than for inflamed eyes (2.39 +/- 0.16 microg*h/mL). In the vitreous humor, corresponding penetrations were 34% and 47%, respectively.


CONCLUSIONS
Penetration of marbofloxacin into the aqueous and vitreous humor after IV administration was significantly enhanced by intraocular inflammation, suggesting a role for this antimicrobial in the prophylaxis or treatment of bacterial endophthalmitis caused by susceptible pathogens.
Regnier
Alain
A
UMR181 Physiopathologie et Toxicologie Expérimentales, INRA, ENVT, Ecole Nationale Vétérinaire,Toulouse Cedex 3, France.
Schneider
Marc
M
Concordet
Didier
D
Toutain
Pierre-Louis
PL
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000187:drug effects; D019540:Area Under Curve; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology*; D004285:Dogs; D009877:Endophthalmitis / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000662:veterinary*; D004926:Escherichia coli / Q000254:growth & development*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000662:veterinary*; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D014822:Vitreous Body / Q000187:drug effects
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C080260:marbofloxacin