Ocular availability of gentamicin in small animals after topical administration of a conventional eye drop solution and a novel long acting bioadhesive ophthalmic drug insert

• Published in: Pharmaceutical research Vol. 12; no. 11; pp. 1791 - 1795
• Main Authors: GURTLER, F, KALTSATOS, V, BOISRAME, B, DELEFORGE, J, GEX-FABRY, M, BALANT, L. P, GURNY, R
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01-11-1995
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria - drug effects; Biological and medical sciences; Biological Assay; Biological Availability; Dogs; Drug Implants; Eye - metabolism; Female; Fluorescence Polarization Immunoassay; Gentamicins - administration & dosage; Gentamicins - pharmacokinetics; Gentamicins - pharmacology; Half-Life; Male; Medical sciences; Ophthalmic Solutions; Pharmacology. Drug treatments; Rabbits; Species Specificity; Tears - metabolism; Tissue Adhesives; Controlled release form; Mucosa; Oral form; Bioavailability; Insert; Adhesion; Eye; Local administration; Antibiotic; Ophthalmic preparation; Aminoglycoside; Antibacterial agent; Comparative study
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1016242528222

Gentamicin eye drop solutions have a short precorneal residence time. The present study investigates the effect of gentamicin using a new long acting delivery Bioadhesive Ophthalmic Insert (BODI) in healthy dogs and rabbits and compares the results with a conventional regimen using an eye drop solution.
In vivo assays were performed on animals after deposition of one BODI and instillations of an eye drop solution. Tear samples were collected over 72 hours and 60 minutes, in the case of inserts and eye drop solution respectively. The gentamicin concentration profiles in tear fluid (determined by a fluorescent polarization immunoassay technique) was individually analyzed, in each animal, in relation with the minimum inhibitory concentration observed in vitro against some bacteria. A non classical pharmacokinetic approach was used for the analysis of the topically applied drug substance, involving two parameters: the efficacy area under the curve (AUCeff) and the efficacy time (teff).
In the case of the eye drop solution, the AUCeff were higher in dogs (2.80 10(3) - 3.64 10(3) [micrograms ml-1 h]) than in rabbits (0.64 x 10(3) - 0.95 x 10(3) [micrograms ml-1 h]); the teff had a similar behavior: 6-15 [h] in dogs and 2-6 [h] in rabbits. In the case of BODIs, the AUCeff and the teff were quite similar between dogs and rabbits: 190 10(3) - 205 10(3) [micrograms ml-1 h] and 70-76 [h], respectively. The AUCeff and the teff were always much higher in the case of BODIs than for the eye drop solution both in dogs and rabbits.
This study shows that topical administration of gentamicin using BODIs can improve treatment due to the decreasing number of applications while ensuring an effective level of antibiotic in tears controlled by the device.