Fukuda Masamichi, Sasaki Hiroshi
Department of Ophthalmology, Kanazawa Medical University, Uchinada, Japan.
Curr Med Res Opin. 2008 Dec;24(12):3479-86. doi: 10.1185/03007990802480091.
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).
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.
The concentration of MFLX was the highest in each tissue, with maximum concentrations of MFLX in the aqueous humor (10.16 +/- 1.59 microg/mL) at 30 min after instillation, cornea (156.07 +/- 95.97 microg/g) and iris/ciliary body (11.92 +/- 4.00 microg/g) at 10 min after instillation, and vitreous body (0.099 +/- 0.033 microg/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 : MIC(90) 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.
AQCmax is a useful pharmacokinetic parameter for determining the therapeutic efficacy of an ophthalmic antibiotic, especially when combined with MIC(90) 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 MIC(90) of S. aureus in all tissues, and MIC(90)s 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 MIC(90)s 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.
摘要 目的：通过最大房水浓度（AQCmax）指标测量并评估五种不同的眼科氟喹诺酮溶液在兔眼中的眼组织渗透情况。
将0.5%莫西沙星（MFLX）、0.5%左氧氟沙星（LVFX）、0.3%加替沙星（GFLX）、0.3%氧氟沙星（OFLX）或0.3%托氟沙星甲苯磺酸盐（TFLX）每隔15分钟滴入白兔眼中，共滴注三次。滴注后10至240分钟收集房水、角膜、虹膜/睫状体和玻璃体，通过高效液相色谱法测量药物浓度。
MFLX在各组织中的浓度最高，滴注后30分钟房水中MFLX的最大浓度为（10.16±1.59微克/毫升），滴注后10分钟角膜中为（156.07±95.97微克/克），虹膜/睫状体中为（11.92±4.00微克/克），滴注后30分钟玻璃体中为（0.099±0.033微克/毫升）。TFLX在各组织中的浓度最低，LVFX、GFLX和OFLX处于中间水平。金黄色葡萄球菌的AQCmax:MIC(90)比值，MFLX为150.67，LVFX为10.6，GFLX为9.69，OFLX为3.48，TFLX无法测定。
AQCmax是确定眼科抗生素治疗效果的有用药代动力学参数，特别是与眼内病原体的MIC(90)值结合使用时。在所研究的五种眼科溶液中，MFLX眼科溶液在所有组织（角膜、房水、虹膜/睫状体和玻璃体）中的C(max)均更优，在所有组织中均超过金黄色葡萄球菌的MIC(90)，在房水、角膜和虹膜/睫状体中超过表皮葡萄球菌、蜡样芽孢杆菌和痤疮丙酸杆菌的MIC(90)。AQCmax在虹膜/睫状体和玻璃体中与C(max)大致成比例，可与MIC(90)结合使用，作为预测眼科抗生素最合适剂量和频率的指标，并结合其他PK/PD参数。本研究可为计算人体中的AQCmax奠定基础。
