Background Intracameral or intracorneal administration of amphotericin B (AMB) can achieve significant therapeutic efficacy in the treatment of recalcitrant fungal keratitis in cases that do not respond to conventional antifungal therapy. However, the ocular pharmacokinetics of the two routes of administration is unclear.Objective The goal of this study was to investigate the level of amphotericin B in cornea and aqueous humor of rabbits after administration of AMB via three different routes. Methods Forty-five healthy domestic rabbits were randomly divided into three groups. 1% amphotericin B of 10 μg was intrastromally or intracamerally injected into 15 rabbits, respectively,in group A and group B. Topical 0. 25% amphotericin B was topically administered to the eyes with corneal epithelial debridement (group C). Experimental animals were sacrificed and the corneas and aqueous humor samples were obtained for the detection of levels of amphotericin B at 30 minutes,6 hours, 1 day,3 and 7 days by high-performance liquid chromatography (HPLC). Results Calibration curves were linear over the range of 0. 10-100. 00 mg/L. The concentration of 0. 10 mg/L was the lowest quantifiable limit. The recovery of amphotericin B ranged from 89. 1% -95.7% from aqueous humor samples and 81.4% -83.6% from the cornea samples. After a single injection,effective drug levels were achieved and maintained for 7 days in cornea in group A, exceeding the minimum inhibitory concentration at which 90% of isolates are inhibited (MIC90) for a wide spectrum of fungi and molds with significant differences in comparison with group B and group C ( P＜0. 05 ). Effective drug levels were achieved in the aqueous humor in group B at 30 minutes after a single injection, but drug levels decreased dramatically within 6 hours. The evident differences were found between group B and group A or group C (P＜ 0.05). A considerable amount of amphotericin B was detected in the cornea and aqueous humor in group C within 1 day.Conclusion Effective high drug levels can be reached in rabbit cornea and aqueous humor after intrastromal and intracameral injection, respectively. Penetration of topical amphotericin B was greatly elevated after epithelial debridement.%背景 角膜基质内注射或前房内注射两性霉素B治疗顽固的真菌性角膜炎取得较好疗效,但通过这2种途径给药后,药物在角膜和房水的浓度变化尚不清楚.目的 探讨质量分数0.25%两性霉素B滴眼液点眼、1%两性霉素B注射液角膜基质内注射及1%两性霉素B注射液前房内注射3种途径给药后兔眼角膜和房水中的药物质量浓度变化.方法 健康家兔45只按随机数字表法分为A、B、C 3组,每组15只.A组、B组分别在角膜基质内和前房内单次注射10 μg两性霉素B注射液,C组兔眼机械法去除角膜上皮后用0.25%两性霉素B滴眼液点眼,每次50μl,共6次,每次间隔5 min.分别于用药后30 min、6 h、1 d、3 d、7 d各处死3只实验兔,获取房水和角膜组织,采用高效液相色谱法进行两性霉素B质量浓度的定量检测.结果 在质量浓度0.10～100.00 mg/L范围内,两性霉素B的峰面积与吸收度之间具有良好的线性关系;0.10mg/L为其定量限质量浓度;药物在房水的回收率为89.1%～95.7%,在角膜中为81.4%～83.6%.用药后30 min、6 h、1 d A组角膜中的药物质量分数高于B组及C组,差异均有统计学意义(P＜0.05),高药物质量浓度可持续7 d,超出绝大多数敏感真菌的MIC90.用药后30 min、6 h、1 d B组兔眼房水中的药物质量浓度高于A组及C组,差异均有统计学意义(P＜0.05).C组1 d内角膜和房水中均检测到明显药物浓度.结论 兔眼角膜基质内注射及前房内注射两性霉素B可以提高药物在角膜及房水中的质量浓度,清除角膜上皮可以提高两性霉素B的角膜穿透力.
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