Measurement of AQCmax of five different ophthalmic solutions and discussion of its new application.
OBJECTIVE
After measuring the pharmacokinetic parameters of five fluoroquinolone ophthalmic solutions, we utilized the obtained indices to try to predict the clinical effects of antimicrobial ophthalmic solutions and apply the characteristics to the index for inhibition of resistant bacteria.


METHODS
Each ophthalmic solution was instilled in white rabbit eyes 3 times every 15 min and the anterior chamber aqueous humor was collected 10, 30, 60, 120, and 240 min after instillation. Drug concentrations were measured by high-performance liquid chromatography (HPLC) to determine the maximum aqueous concentration (AQCmax) of each drug by using a 1-compartment model.


RESULTS
Moxifloxacin (MFLX) had the highest AQCmax, 9.04 microg/mL, among the five drugs, followed by levofloxacin (LVFX, 2.65 microg/mL), gatifloxacin (GFLX, 1.26 microg/mL), ofloxacin (OFLX, 0.89 microg/mL), and tosufloxacin (TFLX, 0.42 microg/mL) in descending order of AQCmax. Furthermore, the AQCmax/MPC (mutant prevention concentration) against Staphylococcus aureus was 15.07 and 1.06 for MFLX and LVFX, respectively. The AQCmax/MPC against Streptococcus pneumoniae was 18.08 and 1.15 for MFLX and LVFX, respectively.


CONCLUSIONS
From these results, we can expect that the MFLX ophthalmic solution will be a sufficiently effective therapeutic agent in the treatment of eye infection, prevention of postoperative endophthalmitis, and prevention of drug resistance.
Fukuda
Masamichi
M
Department of Ophthalmology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. fukuda@kanazawa-med.ac.jp
Sasaki
Hiroshi
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D024881:Drug Resistance, Bacterial; D015818:Eye Infections, Bacterial / Q000188:drug therapy; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008826:Microbial Sensitivity Tests; D009883:Ophthalmic Solutions; D011817:Rabbits; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013997:Time Factors
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D009883:Ophthalmic Solutions