目的探讨布林佐胺噻吗洛尔滴眼液点眼对兔眼玻璃体腔注射万古霉素(VH)后眼内代谢的影响。
方法取普通级健康雄性新西兰白兔9只，其中3只用于抽取空白房水，其余6只以右眼为实验眼，采用布林佐胺噻吗洛尔滴眼液点眼，每日2次，每次30 μl，左眼作为对照眼。分别于首次点眼前和次日点眼后1 h测量双眼眼压。于布林佐胺噻吗洛尔滴眼液点眼第2天，每只实验兔双眼玻璃体腔内各注射VH(10 mg/ml) 0.5 mg。分别于注射后2 h、1 d、2 d、4 d、6 d、8 d、10 d、12 d抽取房水。采用高效液相色谱紫外检测法测定房水中VH的质量浓度，根据平均质量浓度计算VH在兔眼内达峰时间( t max)、达峰浓度( C max)、半衰期( t 1/2)、药时曲线下面积( AUC)。
结果实验眼点眼后眼压值低于点眼前，差异有统计学意义( P<0.01)。实验眼和对照眼房水中VH的 t max均为1 d， C max分别为(61.40±13.48)和(51.56±5.07)μg/ml。注射后4、6和8 d，实验眼房水中VH的质量浓度显著高于对照眼，差异均有统计学意义( t＝2.378、3.150、2.694，均 P<0.05)。实验眼和对照眼VH在房水中代谢的 t 1/2分别为2.69和2.05 d，实验眼 t 1/2相对于对照眼延长了31%。实验眼 AUC 0－10 d相对于对照眼增加了24.3%。
结论布林佐胺噻吗洛尔滴眼液可延长兔眼玻璃体内VH的半衰期。
ObjectiveTo investigate the effect of brinzolamide-timolol maleate eye drops on the metabolism of intravitreally injected vancomycin hydrochloride (VH) in rabbit eyes.
MethodsNine healthy male New Zealand white rabbits were selected.Among them, three were used to extract blank aqueous humor and the right eyes of the remaining six were set as experimental eyes.The experimental eye was topically administered 30 μl of brinzolamide-timolol maleate eye drops twice a day.The fellow eyes were set as control eyes.The intraocular pressure of both eyes was measured before the initial application of the eye drops and 1 hour after application of the eye drops next day.Both eyes of each rabbit were intravitreally injected with 0.5 mg of VH (10 mg/ml) solution.The aqueous humor was drawn at 2 hours and 1, 2, 4, 6, 8, 10 and 12 days after intravitreal injection.VH concentrations in aqueous humor were measured by high performance liquid chromatography.The time of peak concentrations ( t max), peak concentration ( C max), elimination half-life ( t 1/2) and the area under the concentration-time curve ( AUC) of VH in rabbit eyes were calculated by the average concentrations.This study was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-01).
ResultsThe intraocular pressure after eye drop was significantly lower than that before eye drop in experimental eyes ( P<0.01).The t max of VH in experimental eyes and control eyes were both 1 day.The C max of VH in experimental eyes and control eyes were (61.40±13.48) and (51.56±5.07)μg/ml, respectively.The VH aqueous concentrations in the experimental eyes on days 4, 6 and 8 after injection were all significantly higher than those in the control eye ( t=2.378, 3.150, 2.694; all P<0.05).The t 1/2 of VH in the aqueous humor of the experimental eyes was 2.69 days, which was 31% longer than 2.05 days of the control eyes.The AUC 0-10 d of experimental eyes increased by 24.3% relative to the control eyes.
ConclusionsBrinzolamide-timolol maleate eye drops can significantly extend the ocular residence time of intravitreally injected VH.
周天洋,杨晶晶,李翔,等. 布林佐胺噻吗洛尔滴眼液对兔眼内万古霉素代谢的影响[J]. 中华实验眼科杂志,2025,43(01)：27-31.
DOI:10.3760/cma.j.cn115989-20240410-00102版权归中华医学会所有。
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周天洋：酝酿和设计实验、实施研究、采集数据、分析/解释数据、起草文章；杨晶晶、夏慧芸：实施研究、采集数据、分析/解释数据；李翔：实施研究、分析/解释数据；何继军：实施研究、采集数据；张俊杰：酝酿和设计实验、分析/解释数据、对文章的知识性内容作批评性审阅及定稿
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