Calculation of AQCmax: comparison of five ophthalmic fluoroquinolone solutions

ABSTRACT

Objective: 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. C_max 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 C_max 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.

Key words: :

• AQCmax
• Aqueous concentration
• Fluoroquinolone
• Gatifloxacin
• Levofloxacin
• Moxifloxacin
• Ofloxacin
• Tosufloxacin tosilate

Acknowledgement

Declaration of interest: This research was supported by Alcon Japan Ltd, with medical writing assistance from Christina Ohnsman, MD, an ophthalmologist in Reading, PA, USA.

Notes

* Data in this paper were presented at the Association for Research in Vision and Ophthalmology, May 9, 2007, Ft. Lauderdale, FL, USA