摘要
目的探讨1％伏立康唑滴眼液在兔眼角膜的渗透性及其局部应用的角膜与房水药物代谢动力学变化。方法为实验研究。选择健康的成年新西兰白兔48只，采用单纯随机数字表法分为A、B及C组。1％伏立康唑单次50山滴人A组（角膜上皮完整组，21只）和B组（去角膜上皮组，21只）兔双眼结膜囊，分别于用药后2、5、10、15、30、60及90min处死动物取材；取C组（未用药组，6只）兔眼样品用于方法学验证。获取的房水和角膜样品采用高效液相色谱法（HPLC）进行定量检测。色谱条件为：高效液相色谱议为Waters1525色谱系统，Phenomenex Luna C18（250．0mm×4．6mm，5．0μm）分析柱，预柱为Phenomenex C18（4．0mm×3．0mm，5．0μm），流动相为甲醇-0．04moL／L磷酸二氢铵缓冲液（62：38，V／V），流速为0．8ml／min，紫外检测波长为255．0nm，采用外标法进行定量。用非线性最小二乘法进行计算机拟合求得药物代谢动力学参数。结果在0．1—15．0mg／L范围内，伏立康唑的峰面积与其吸收度之间具有较好的线性关系；O．1mg／L为其定量限浓度；房水的药物回收率范围在91．06％一94．80％，角膜为79．84％-83．20％。1％伏立康唑单剂量滴眼在A组和B组的房水峰浓度时间均为10min，分别为（5．172±1．012）mg／L和（6．118±1．123）mg／L；药物的消除半衰期（t1/2ke）分别为6．859min和13．176min；两组的角膜药物浓度在2min时最高，分别为（39．958±3．481）μg,／g和（158．476±10．462）μg,／g；药物的消除半衰期（t1／2β）分别为94．938min和46．367min。结论1％伏立康唑滴眼液局部应用的组织穿透性好，单次滴眼在角膜和房水中均达到了较高的药物浓度，对临床上治疗真菌性角膜溃疡具有重要的意义。
Objective To investigate the penetration of topical 1% voriconazole into the cornea and aqueous humor in New Zealand white rabbits. Methods It was a experimental study. Forty-eight healthy rabbits were randomly divided into groups A （21 cases）, B （21 cases） and C （6 cases）. Blank samples from group C were used to determine the essential parameters for the validation of analytical procedures. A single 50 μl drop of 1% voriconazole was administered in group A （ non-debrided cornea） and group B （ debrided cornea）. The aqueous humor and the cornea were obtained at 2, 5, 10, 15, 30, 60 and 90 rain after application. All samples were analyzed by high-performance liquid chromatography （HPLC）. The HPLC system consisted of Waters 1525 pump, Phenomenex Luna Cls （ 250. 0 mm × 4. 6 mm, 5.0 μm） column, Phenomenex Cls （4. 0 nun ×3.0 mm, 5.0 μm） analytical steel column and a Waters Empower data workstation. The UV detector was set to 255. 0 nm. Methanol-0. 04 mol/L ammonium hydroxide （62： 38, V/V） was used as mobile phase and the flow rate was 0. 8 ml/min. External standard was used in this assay. The pharrnacokinetic parameters were calculated with nonlinear least square method by the computer. Results Calibration curves were linear over the range 0. 1 ~ 15.0 mg/L. The concentration at 0. 1 mg/L was the lowest quantified limit. The recovery of voriconazole from aqueous humor samples ranged from 91.06% to 94. 80%, and ranged from 79. 84% to 83. 20% in the cornea samples. After single dose application, the drug concentration in aqueous humor peaked at 10 min in both group A [ （5. 172 ± 1. 012） mg/L] and group B [ （6. 118 ± 1. 123） mg/L], and the parameters t,/2 ke in groups A and B were 6. 859 min and 13. 176 min, respectively. However, peak drug levels were achieved immediately at 2 min in the cornea [group A： （9. 958 ± 3.481 ） I-tg/g and group B： （ 158. 476 ± 10. 462） μg/g]. The parameter t,/2tβ in nondebrided cornea was 94. 938 min and 46. 367 min in debride
出处
《中华眼科杂志》
CAS
CSCD
北大核心
2008年第4期349-353,共5页
Chinese Journal of Ophthalmology
基金
卫生部临床研究重点项目基金资助项目（20013955）
关键词
三唑类
嘧啶类
眼药水
色谱法
高效液相
药物代谢动力学
Triazoles
Pyrimidines
Ophthalmic solutions
Chromatography, high pressure liquid
Pharmacokinetics
