Ocular Pharmacokinetics/Pharmacodynamics of Besifloxacin, Moxifloxacin, and Gatifloxacin Following Topical Administration to Pigmented Rabbits

Abstract Purpose: The purpose of this investigation was to evaluate the ocular pharmacokinetic/pharmacodynamic (PK/PD) relationship for besifloxacin, moxifloxacin, and gatifloxacin using rabbit ocular PK data, along with in vitro minimum inhibitory concentration (MIC90) values against methicillin- and ciprofloxacin-resistant Staphylococcus aureus (MRSA-CR) and Staphylococcus epidermidis (MRSE-CR). Methods: Rabbits received a topical instillation of Besivance™ (besifloxacin ophthalmic suspension, 0.6%), Vigamox® (moxifloxacin hydrochloride ophthalmic solution, 0.5% as base), or Zymar® (gatifloxacin ophthalmic solution, 0.3%), and ocular tissues and plasma were collected from 4 animals/treatment/collection time at 8 predetermined time intervals during the 24 h after dosing. Ocular levels of each agent were measured by LC/MS/MS, and PK parameters (Cmax, Tmax, and AUC0–24) were determined. AUC0–24/MIC90 ratios were calculated for tears, conjunctiva, cornea, and aqueous humor using previously reported MIC90 va...