氟康唑眼液滴眼的眼内药代动力学实验研究

Pharmacokinetics of topically applied fluconazole in the rabbit eye

目的 研究 0 5 %氟康唑滴眼液在兔角膜的渗透性及其在角膜和房水中的药代动力学行为。方法 将新西兰大白兔双眼滴入 0 5 %氟康唑眼液后 ,分别于不同时间处死家兔 ,将获取的房水和角膜组织用反相高效液相色谱法 (highperformanceliquidchromatography ,HPLC)进行定量测定。色谱条件 :色谱柱为SpherisorbC18,粒径为 5 μm ,色谱柱长度和直径为 2 0 0 0mm× 4 6mm ,柱温为 4 5℃ ,流动相为 0 0 5mol/L磷酸二氢钾 甲醇 (6 5∶35 ) ,流速为 1ml/min ,检测波长为 2 6 5nm。采用非线性最小二乘法进行计算机拟合求得药代动学参数。结果 采用反相HPLC法可以将氟康唑同其他杂质很好分离 ,最低定量浓度为 0 1mg/L ,氟康唑在组织中的回收率平均为 90 6 %。 0 5 %氟康唑滴眼后的各时间点角膜组织及房水中均可检测出氟康唑的含量 ,其中角膜组织中于滴药后 2min时含量最高为 (15 2 0± 1 95 ) μg/g ,房水中 15min时的含量最高为 (2 39± 0 92 )mg/L。角膜上皮渗透系数为1 0 6× 10 -5。角膜组织中药物浓度半衰期为 6 3 96min ,房水中为 4 2 14min。结论 氟康唑可用于真菌性角膜炎的局部抗真菌治疗 。

Objective To observe the penetration of 0 5% fluconazole (FCZ) into the corneas and aqueous humors of New Zealand white rabbits following its topical application. Methods The rabbit corneas and aqueous humors were obtained and quantified at different times after topically applying 0 5% FCZ to the rabbit eyes. The drug levels were assayed by high performance liquid chromatography (HPLC). The pharmacokinetic parameters were calculated with nonlinear least square method by the computer. Results FCZ can rapidly penetrate into rabbit corneas. Peak corneal levels occurred essentially immediately at 2 min in the corneas (15 20±1 95) μg/g and at 15 min after application in the aqueous (2 39±0 92 mg/L). The permeability of the corneal epithelial barrier (Kep) was 1 06×10 -5 . The half life (t l/2 ) of the cornea was 63 96 min, and that of the aqueous humor was 42 14 min. Conclusion Topical fluconazole can be used as a topical antifungal agent to treat keratitis and needs further evaluation for treating fungal endophthalmitis.