Fukuda Masamichi, Sasaki Hiroshi
Department of Ophthalmology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
J Ocul Pharmacol Ther. 2009 Aug;25(4):351-6. doi: 10.1089/jop.2008.0032.
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.
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.
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.
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.
在测定了五种氟喹诺酮类眼药水的药代动力学参数后，我们利用所得指标尝试预测抗菌眼药水的临床效果，并将这些特性应用于抑制耐药菌的指标。
每隔15分钟给白兔眼滴注一次每种眼药水，共滴注3次，滴注后10、30、60、120和240分钟收集前房房水。采用高效液相色谱法（HPLC）测定药物浓度，通过一室模型确定每种药物的最大房水浓度（AQCmax）。
在这五种药物中，莫西沙星（MFLX）的AQCmax最高，为9.04微克/毫升，其次是左氧氟沙星（LVFX，2.65微克/毫升）、加替沙星（GFLX，1.26微克/毫升）、氧氟沙星（OFLX，0.89微克/毫升）和妥舒沙星（TFLX，0.42微克/毫升），AQCmax依次递减。此外，MFLX和LVFX对金黄色葡萄球菌的AQCmax/MPC（突变预防浓度）分别为15.07和1.06。MFLX和LVFX对肺炎链球菌的AQCmax/MPC分别为18.08和1.15。
从这些结果可以预期，莫西沙星眼药水在治疗眼部感染、预防术后眼内炎和预防耐药性方面将是一种足够有效的治疗药物。
