Ben-Nun J, Joyce D A, Cooper R L, Cringle S J, Constable I J
Sir Charles Gairdner Hospital, Western Australia.
Invest Ophthalmol Vis Sci. 1989 Jun;30(6):1055-61.
Intravitreal drug administration is the treatment of choice for bacterial endophtalmitis, but improved knowledge of vitreal pharmacokinetics is essential for the development of optimal antibiotic regimes. We used our recently developed sampling device to estimate vitreal gentamicin concentrations for up to 30 hr after an intravitreal bolus injection of gentamicin. The device is based on the principle of dialysis, whereby a constant flow rate of dialysate through a loop of dialysis fiber in the vitreous attains a gentamicin concentration proportional to the intravitreal gentamicin level around the fiber. The dialysate is continuously recovered and the collected samples then assayed for gentamicin. Normal cat eyes and those with induced bacterial endophthalmitis formed the two groups tested. Concentration-time data fitted well to an open single compartment pharmacokinetic model that incorporated the processes of transfer of drug from the injection site to the sampling site (a function of diffusion within the vitreous), and the elimination from the sampling site (a function of elimination from the vitreous). The initial phase of transfer between the injection and sampling site was rapid and rates were comparable in the two groups. Elimination rate constants were uniformly greater in infected eyes than in controls (0.107 hr-1 compared to 0.055 hr-1). Aqueous humor gentamicin concentrations in control eyes varied between 3 and 6 times those found in fellow infected eyes at the end of each experiment. Accelerated elimination of gentamicin from the vitreous body of eyes with endophthalmitis may be explained by increased permeability of the blood-retinal barrier.
玻璃体内给药是细菌性眼内炎的首选治疗方法，但深入了解玻璃体内药代动力学对于制定最佳抗生素治疗方案至关重要。我们使用最近开发的采样装置，在玻璃体内一次性注射庆大霉素后，估计长达30小时的玻璃体内庆大霉素浓度。该装置基于透析原理，即通过玻璃体内透析纤维环的透析液恒定流速可获得与纤维周围玻璃体内庆大霉素水平成比例的庆大霉素浓度。透析液被持续回收，然后对收集的样品进行庆大霉素检测。正常猫眼和诱导性细菌性眼内炎的猫眼构成了两个测试组。浓度 - 时间数据很好地拟合了一个开放的单室药代动力学模型，该模型纳入了药物从注射部位转移到采样部位的过程（玻璃体内扩散的函数）以及从采样部位消除的过程（玻璃体内消除的函数）。注射部位和采样部位之间转移的初始阶段很快，两组的速率相当。感染眼的消除速率常数始终高于对照组（分别为0.107小时⁻¹和0.055小时⁻¹）。在每个实验结束时，对照眼中房水庆大霉素浓度是感染眼的3至6倍。眼内炎患者玻璃体内庆大霉素消除加速可能是由于血 - 视网膜屏障通透性增加所致。
