title: Comparison between intracameral moxifloxacin administration methods by assessing intraocular concentrations and drug kinetics.
abstract: BACKGROUND
  Studies have indicated that intracameral administration of moxifloxacin (MFLX), a fourth-generation fluoroquinolone, is safe and effective. However, administration methods vary between studies, and no definite protocol exists. A prospective study clarifying the incidence of endophthalmitis and complication rates associated with each administration method would require an extremely large sample size because endophthalmitis has a low incidence rate. Therefore, we investigated appropriate intracameral MFLX administration methods by assessing intraocular concentrations following simple injection and flushing, and by measuring drug kinetics (half-life).
  
  
  METHODS
  Experiment 1: (human eyes). Irrigation (flushing) with 33.33 μg/ml MFLX (150-fold dilution) and simple injection with 0.1 ml of 500 μg/ml MFLX (10-fold dilution) were assessed after cataract surgery. Experiment 2: (rabbits: kinetics study). Flushing with 30-fold or 150-fold dilutions of MFLX was assessed. Aqueous humor samples (0.1 ml) obtained immediately after irrigation and 1, 3, and 5 h after irrigation were analyzed using high-performance liquid chromatography.
  
  
  RESULTS
  Experiment 1: MFLX (500 μg/ml) administered using simple injection in humans underwent a 3.3-fold dilution (152.33 μg/ml). Total anterior chamber displacement after flushing with 33.33 μg/ml MFLX resulted in a concentration of 29.54 μg/ml (90% displacement). Experiment 2: Concentrations at baseline were 52% at 1 and 15% at 3 h respectively, suggesting that the half-life of intracameral MFLX was >1 h.
  
  
  CONCLUSIONS
  Considering that the half-life of MFLX was >1 h, a final concentration of 150 μg/ml results in a 2 h concentration of 38 μg/ml, which was beyond the minimum inhibitory concentration required to inhibit the growth of 90% of bacteria (MIC90) for most resistant pathogens. We postulate that a final concentration of 150 μg/ml is considerably effective and safe. However, more resistant bacteria will evolve in the future, and the standard MIC90 may change accordingly. Therefore, even if a suitable concentration is determined, it may not necessarily remain constant. This effective concentration should be continually revised on the basis of safety and effectiveness assessments.
authors.affiliation: Nojima Hospital, 2714-1, Sesaki-machi, Kurayoshi-city, Tottori 682-0863, Japan. i-mnys2001@za.ztv.ne.jp
authors.forename: Kazuki
authors.initials: K
authors.lastname: Matsuura
authors.forename: Chikako
authors.initials: C
authors.lastname: Suto
authors.forename: Junsuke
authors.initials: J
authors.lastname: Akura
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Inoue
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001372:Aza Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002387:Cataract Extraction; D002851:Chromatography, High Pressure Liquid; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D056965:Injections, Intraocular; D007700:Kinetics; D019654:Lens Implantation, Intraocular; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D011446:Prospective Studies; D011804:Quinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011817:Rabbits
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin
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