两性霉素B脂质体滴眼液在兔房水中的药动学

目的:探索兔眼局部应用生物黏附性两性霉素B脂质体(AmBL)滴眼液后,房水中的药动学状况。方法:32只新西兰白兔,在角膜上皮完整和刮除时,分别应用0．5％AmBL滴一眼,用0．5％两性霉素B滴眼液(AmBS)滴对侧眼作对照,于用药后0．25,0．5,1,2,3和4 h的6个时点,选取不同的白兔抽取房水,用高效液相色谱法测定房水中AmB的含量。结果:AmBL滴眼后,房水中AmB的有效抑菌浓度可维持2 h,AmBE S滴眼1 h后即近全部消除。角膜上皮完整时,AmBL的AUC和t1/2是AmBS的3．6倍和5倍;角膜上皮刮除后,AmBL的AUC和t1/2是AmBL S的3．9倍和3．2倍。结论:0．5％AmBL滴眼液具有较好的缓释作用和生物利用度,药物浓度较稳定,作用时间较长,是较有前途的局部治疗真菌性角膜炎的新型缓释制剂。

Pharmacokinetics of amphotericin B liposome eye drop in aqueous humor of rabbit

AIM: To investigate the pharmacokinetics of tropically administered bioadhesive amphotericin B liposome (AmBL) in aqueous humor of rabbit. METHODS: In 32 rabbits with and without comeal epitheli- um, 0.5 % AmBL was applied tropically in one eye, with 0.5 % amphotericin B eye drop (AmBS) as control in the contralateral eye. Aqueous humor was sampled by aspiration after 0.25, 0.5, 1, 2, 3 and 4 h from different rabbits and AmB concentration was determined by HPLC. RESULTS: After tropical administration of AmBL, aqueous AmB concentration could maintain above and around MIC for about 2 h, while the AmB concentration after using AmBS was far below the MIC at 1 h point and afterwards. With the presence of the corneal epithelial, the A UC and t1/2 of AmBL were about 3.6 and 5 times as high as those of AmBS, respectively; without the presence of the corneal epithelial, the A UC and t1/2 of AmBL were about 3.9 and 3.2 times as high as those of AmBS, respectively. CONCLUSION: AmBL was an promising sustained releasing agent with relatively stable drug concentratin, high bioavailability and prolonged effective time for tropical administration in fungal keratitis.