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Pharmacokinetics of intravitreal injection. Assessment of a gentamicin model by ocular dialysis
J Ben-Nun1, D A Joyce, R L Cooper
1Sir Charles Gairdner Hospital, Western Australia.
Abstract:
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.
Insights
Bacterial endophthalmitis accelerates gentamicin elimination from the vitreous. This study developed a dialysis device to measure drug levels, crucial for optimizing antibiotic treatments for this severe eye infection.
Area of Science:
- Ophthalmology
- Pharmacokinetics
- Microbiology
Background:
- Intravitreal antibiotic injection is standard for bacterial endophthalmitis.
- Understanding vitreous pharmacokinetics is key to effective antibiotic regimens.
- Current methods for measuring intraocular drug levels are limited.
Purpose of the Study:
- To quantify intravitreal gentamicin concentrations over time after injection.
- To compare gentamicin pharmacokinetics in normal versus infected feline eyes.
- To assess the utility of a novel dialysis-based sampling device for vitreous drug measurement.
Main Methods:
- A novel dialysis device was used to sample vitreous fluid in cats.
- Gentamicin concentrations were measured for up to 30 hours post-injection.
- Pharmacokinetic analysis was performed using a single-compartment model.
- Two groups were studied: normal eyes and eyes with induced bacterial endophthalmitis.
Main Results:
- The developed device accurately measured intravitreal gentamicin concentrations.
- Gentamicin elimination was significantly faster in eyes with bacterial endophthalmitis (0.107 hr-1) compared to normal eyes (0.055 hr-1).
- Aqueous humor gentamicin levels were higher in control eyes than in infected eyes.
Conclusions:
- Bacterial endophthalmitis accelerates gentamicin elimination from the vitreous, likely due to increased blood-retinal barrier permeability.
- The developed dialysis device is effective for pharmacokinetic studies of intravitreal drugs.
- Findings support the need for adjusted antibiotic dosing strategies in bacterial endophthalmitis.