Comparison between intracameral moxifloxacin administration methods by assessing intraocular concentrations and drug kinetics
Comparison between intracameral moxifloxacin administration methods by assessing intraocular concentrations and drug kinetics
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DOI：
10.1007/s00417-013-2294-7
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发表时间：
2013-08-01
影响因子：
2.7
通讯作者：
Inoue, Yoshitsugu
中科院分区：
文献类型：
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作者：
Matsuura, Kazuki;Suto, Chikako;Inoue, Yoshitsugu
研究表明，第四代氟喹诺酮类药物莫西沙星(MFLX)腔内给药安全有效。然而，不同研究的给药方法各不相同，也没有明确的方案存在。由于眼内炎的发病率较低，一项明确每种给药方法相关的眼内炎发病率和并发症发生率的前瞻性研究需要极大的样本量。因此，我们通过评估简单注射和冲洗后的眼内浓度，以及通过测量药物动力学(半衰期)来研究合适的MFLX房内给药方法。术后分别用33.33mU g/mlMFLX(150倍稀释液)和0.1ml500 mU g/mlMFLX(10倍稀释度)进行冲洗。实验2：(兔：动力学研究)。用30倍或150倍的甲氟沙星稀释冲洗进行评估。分别于冲洗后即刻、冲洗后1、3、5h取房水样品0.1ml，用高效液相色谱法进行分析。实验1：人单纯注射甲氟沙星(500mU g/ml)后，将其稀释3.3倍(152.33 mU g/ml)。33.33微克/毫升甲氟沙星冲洗后前房总移位为29.54微克/毫升(90%移位)。实验2：基线浓度分别为52%(1h)和15%(3h)，表明Mflx在房内的半衰期为1h。考虑到Mflx的半衰期为1h，最终浓度为150mU g/ml，2 h的浓度为38mU g/ml，超过了对大多数耐药病原菌抑制90%细菌生长所需的最低抑菌浓度(MIC90)。我们推测，150微克/毫升的最终浓度是相当有效和安全的。然而，未来将进化出更多抗药性细菌，标准MIC90可能会相应改变。因此，即使确定了合适的浓度，它也不一定保持不变。这一有效的集中度应在安全和有效性评估的基础上不断修订。
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).Experiment 1: (human eyes). Irrigation (flushing) with 33.33 mu g/ml MFLX (150-fold dilution) and simple injection with 0.1 ml of 500 mu g/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.Experiment 1: MFLX (500 mu g/ml) administered using simple injection in humans underwent a 3.3-fold dilution (152.33 mu g/ml). Total anterior chamber displacement after flushing with 33.33 mu g/ml MFLX resulted in a concentration of 29.54 mu g/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.Considering that the half-life of MFLX was > 1 h, a final concentration of 150 mu g/ml results in a 2 h concentration of 38 mu g/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 mu g/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.