Calculation of AQCmax: comparison of five ophthalmic fluoroquinolone solutions

Abstract

ABSTRACTObjective: Ocular tissue penetration of five different ophthalmic fluoroquinolone solutions in the rabbit eye was measured and evaluated by an index of the maximum aqueous concentration (AQCmax).Methods: Moxifloxacin 0.5% (MFLX), levofloxacin 0.5% (LVFX), gatifloxacin 0.3% (GFLX), ofloxacin 0.3% (OFLX), or tosufloxacin tosilate 0.3% (TFLX) were instilled into the eyes of white rabbits every 15 min for a total of three doses. Aqueous humor, cornea, iris/ciliary body and vitreous body were collected 10 to 240 min after instillation and drug concentrations were measured by high-performance liquid chromatography.Results: The concentration of MFLX was the highest in each tissue, with maximum concentrations of MFLX in the aqueous humor (10.16 ± 1.59 µg/mL) at 30 min after instillation, cornea (156.07 ± 95.97 µg/g) and iris/ciliary body (11.92 ± 4.00 µg/g) at 10 min after instillation, and vitreous body (0.099 ± 0.033 µg/mL) at 30 min after instillation. The concentration of TFLX was the lowest in each tissue, with LVFX, GFLX, and OFLX sharing the mid-ranks. AQCmax : MIC90 ratio for S. aureus was 150.67 for MFLX, 10.6 for LVFX, 9.69 for GFLX, 3.48 for OFLX, and could not be determined for TFLX.Conclusion: AQCmax is a useful pharmacokinetic parameter for determining the therapeutic efficacy of an ophthalmic antibiotic, especially when combined with MIC90 values for intraocular pathogens. Cmax of MFLX ophthalmic solution was superior in all tissues (cornea, aqueous humor, iris/ciliary body and vitreous body) among the five ophthalmic solutions studied, exceeding the MIC90 of S. aureus in all tissues, and MIC90s of S. epidermidis, B. cereus, and P. acnes in aqueous humor, cornea, and iris/ciliary body. AQCmax was approximately proportional to Cmax in iris/ciliary body and vitreous, and may be used in combination with MIC90s as an index to predict the most appropriate dose and frequency of ophthalmic antibiotics in conjunction with other PK/PD parameters. This study may provide the groundwork for calculation of AQCmax in humans.