Ofloxacin otic solution in patients with otitis media - An analysis of drug concentrations
Ofloxacin otic solution in patients with otitis media - An analysis of drug concentrations
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DOI：
10.1001/archotol.125.3.337
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发表时间：
1999-03-01
影响因子：
--
通讯作者：
Miyazaki, Y
中科院分区：
文献类型：
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作者：
Ohyama, M;Furuta, S;Miyazaki, Y
目的：测定局部给予 0.3% 氧氟沙星滴耳液后耳漏、血清和中耳粘膜中氧氟沙星的浓度。 设计：对患有慢性化脓性中耳炎和鼓膜穿孔的儿童单剂量 0.5 mL 或 0.25 mL 给予 0.3% 氧氟沙星滴耳液的研究，在滴耳后 8 小时内连续采样耳漏和血清。给药后 2 小时内对给药和中耳粘膜进行检测。地点：日本鹿儿岛的三家医院。患者：38 名患有慢性化脓性中耳炎和鼓膜穿孔的患者（年龄范围，3-81 岁）； 20 名患者进行了耳漏和血清采样，18 名患者（需要中耳手术）进行了中耳粘膜和血清采样。 结果：给药后立即采集的耳漏样本中检测到高浓度的氧氟沙星，随后呈快速、非对数下降。通过耳漏消除药物被认为与耳部引流从应用部位的流失有关，而不是与生物机制有关。耳漏中氧氟沙星的最大浓度出现在给药后 30 分钟的初始采样时间，并在 8 小时时测量到最后一次采样的浓度。局部给药后，血清中氧氟沙星浓度极低。大多数患者的血清样本中未检测到浓度。测得的最高浓度为 10 ng/mL。主要在给药后 1 小时内获得的样品中检测药物浓度。粘膜药物浓度变化很大，范围从不可检测到 602 μg/g。对于从中耳分离的 6 种细菌菌株，氧氟沙星的最高最低抑菌浓度被一些患者用药后 8 小时内测量的耳漏药物浓度覆盖。没有观察到不良事件。实验室测试结果或听力测试结果未观察到有临床意义的不良变化。结论：耳漏中的药物浓度较高，血清中的药物浓度很低或未检测到，中耳粘膜中的药物浓度变化很大。通过外耳道和咽鼓管进行耳部引流时药物的非生物损失可能与耳漏样本中的高浓度有关。中耳粘膜中的药物浓度表明药物已到达感染部位。
Objective: To measure the concentration of ofloxacin in otorrhea, serum, and middle ear mucosa after topical administration of 0.3% ofloxacin otic solution.Design: Study of 0.3% ofloxacin otic solution administered in a single dose of 0.5 mL in adults or 0.25 mL in children with chronic suppurative otitis media and perforated tympanic membrane, with serial sampling of otorrhea and serum up to 8 hours after dosing and middle ear mucosa up to 2 hours after dosing.Setting: Three hospitals in Kagoshima, Japan.Patients: Thirty-eight patients (age range, 3-81 years) with chronic suppurative otitis media and perforated tympanic membrane; 20 patients had sampling of otorrhea and serum and 18 patients (who required middle ear surgery) had middle ear mucosa and serum sampling.Results: High concentrations of ofloxacin were measured in otorrhea samples taken immediately after dosing, followed by a rapid, nonlogarithmic decline. Elimination of the drug through otorrhea was believed to be related to loss from the application site with ear drainage, rather than to biologic mechanisms. Maximum concentration of ofloxacin in otorrhea was seen at the initial sampling time, 30 minutes after dosing, with concentrations measured up to the last sampling at 8 hours. Very low concentrations of ofloxacin were found in serum after topical administration of the drug. Concentrations were not detected in serum samples of most of the patients. The highest concentration measured was 10 ng/mL. Drug concentrations were detected primarily in samples obtained up to 1 hour after the dose was administered. Mucosal drug concentrations were highly variable, ranging from nondetectable to 602 mu g/g. For the 6 bacterial strains isolated from the middle ear, the highest minimum inhibitory concentration of ofloxacin was covered by otorrhea drug concentrations measured at up to 8 hours after dosing in some patients. No adverse events were observed. No clinically significant adverse changes in laboratory test results or audiometric results were observed.Conclusions: Drug concentrations were high in otorrhea, very low or not detected in serum, and highly variable in middle ear mucosa. Nonbiologic loss of the drug with the ear drainage through the external auditory canal and eustachian tube was probably related to the high concentration in otorrhea samples. Drug concentrations in middle ear mucosa suggest that the drug reaches the infection site.