Effect of inflammation on antibiotic penetration into the anterior segment of the rat eye.
Bacterial infections were established in the right cornea of rats. Animals infected with Staphylococcus aureus were given cephradine intravenously (IV) (40 mg/kg) or topically (50 mg/ml) to both eyes. Animals infected with Pseudomonas aeruginosa were given gentamicin sulfate IV (40 mg/kg) or topically (10 mg/ml). Antibiotic concentrations in cornea and aqueous humor were measured for 4 hrs following dosing using bioassay and radioimmunoassay. In general, infection significantly increased the concentrations obtained soon after dosing. Topically applied cephradine passed through infected eyes more quickly than through normal eyes. Of the pharmacokinetic parameters derived, the permeability of the corneal epithelium to gentamicin in the rat more closely agrees with reported human values than does the rabbit, while the coefficient of elimination from aqueous in the rat is considerably greater than that for either humans or rabbits. This suggests that there are both advantages and disadvantages in using the rat for therapeutic studies of ocular disease.
P R
PR
Badenoch
P J
PJ
McDonald
D J
DJ
Coster
D000287:Administration, Topical; D000818:Animals; D000869:Anterior Eye Segment / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism*; D002511:Cephalosporins / Q000378:metabolism*; D002515:Cephradine / Q000008:administration & dosage / Q000378:metabolism*; D005839:Gentamicins / Q000008:administration & dosage / Q000378:metabolism*; D007275:Injections, Intravenous; D007634:Keratitis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D010539:Permeability; D011552:Pseudomonas Infections; D051381:Rats / Q000378:metabolism*; D011919:Rats, Inbred Strains; D013203:Staphylococcal Infections
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005839:Gentamicins; D002515:Cephradine