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J Ben-Nun, D A Joyce, R L Cooper, S J Cringle, I J Constable; Pharmacokinetics of intravitreal injection. Assessment of a gentamicin model by ocular dialysis.. Invest. Ophthalmol. Vis. Sci. 1989;30(6):1055-1061.
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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.
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