兔眼玻璃体腔注射替考拉宁眼内药代动力学研究

摘要

Background Endophthalmitis is a serious infectious eye disease.Efficient drug therapy plays a key role in the early stage.There have been few researches on teicoplanin treating endophthalmitis and pharmacokinetics in ocular tissue.Objective The present study was to investigate the intraocular pharmacokinetic course and feature of intravitreal administration of teicoplanin.Methods Thirty-three Japanese white rabbits were included in this study and randomized into 6 groups.The right eyes of the rabbits were used in experiment.5 g/L of teicoplanin was injected into the vitreous cavity,and vitreous and aqueous humor samples were extracted after 15 minutes,30 minutes,1,2,4,6,12,24,48,96 and 192 hours,and the concentration of teicoplanin was determined by bioassay.Results The logarithmic value of the concentration of teicoplanin was raised with the increase in the bacterial inhibition zone diameters,of which the equation of the regression curve was Y =0.174X-0.813(R2=0.999).A good linear relationship was presented within 1.0-80.0 mg/L.Single intravitreal injection of teicoplanin was compliant with the two-compartment model.Moreover,the distribution phase Tα1/2 and elimination phase Tβ1/2 of vitreous were 1.68 and 152.15 hours,separately.And Tα1/2 and Tβ1/2 of the aqueous humor were 2.83 hours and 70.56 hours,individually.The peak teicoplanin concentrations in the vitreous and aqueous humor were(358.47±21.53)mg/L and(102.17±9.54)mg/L at 1 hour,respectively and remained at(4.38±0.68)mg/L and(2.38±0.38)mg/L,respectively 192 hours later.Conclusions Intravitreal injection of 0.5 mg of teicoplanin can remain therapeutic concentration for a long time in the vitreous and aqueous humor.%背景 眼内炎是严重的感染性眼病,早期有效的药物治疗至关重要.替考拉宁眼内用药治疗眼内炎及眼内药代动力学方面的研究文献报道较少.目的 探讨兔眼玻璃体腔注射替考拉宁眼内药代动力学过程及特点.方法 取日本大耳白兔33只,右眼玻璃体腔注射替考拉宁0.5 mg后,分别于15 min、30 min和1、2、4、6、12、24、48、96、192 h抽取玻璃体及房水各0.1ml,采用微生物检定法测定替考拉宁的质量浓度.结果 替考拉宁标准品质量浓度的对数值随着抑菌圈直径的增加而增加,其标准品回归曲线方程:Y=0.174X-0.813(R2 =0.999),在替考拉宁质量浓度为1.0-80.0 mg/L范围内线性关系良好.替考拉宁玻璃体腔单次注射符合开放性二室模型,玻璃体腔分布相Tα1/2与消除相Tβ1/2分别为1.68 h、152.15 h,房水中分布相T1/2与消除相Tβ1/2分别为2.83 h、70.56h.替考拉宁在玻璃体、房水中的峰质量浓度分别为(358.47±21.53)mg/L、(102.17±9.54)mg/L,达峰时间分别为1h；在192 h时,玻璃体、房水中替考拉宁质量浓度分别为(4.38±0.68)mg/L、(2.38±0.38)mg/L.结论 替考拉宁0.50 mg玻璃体腔注射后能在玻璃体、房水中维持较长时间的药物治疗质量浓度.