In Vivo/in Vitro Correlation of Intravitreal Delivery of Drugs with the Help of Computer Simulation.

Ohtori, Akira; Tojo, Kakuji

doi:10.1248/bpb.17.283

Cited by 48 publications

(24 citation statements)

References 1 publication

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“…Ohtori and Tojo 30 reported a computer simulation of drug delivery to the eye from intravitreal injections using dexamethasone sodium m-sulfobenzoate (DMSB) as the model drug. They concluded that the major route of elimination was via the posterior aqueous humor, especially for hydrophilic drugs, but that the RCS membrane, because of its large area, cannot be overlooked, especially for lipophilic drugs.…”

Section: Discussionmentioning

confidence: 99%

Study of Ocular Transport of Drugs Released from an Intravitreal Implant Using Magnetic Resonance Imaging

et al. 2005

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Ensuring optimum delivery of therapeutic agents in the eye requires detailed information about the transport mechanisms and elimination pathways available. This knowledge can guide the development of new drug delivery devices. In this study, we investigated the movement of a drug surrogate, Gd-DTPA (Magnevist) released from a polymer-based implant in rabbit vitreous using T1-weighted magnetic resonance imaging (MRI). Intensity values in the MRI data were converted to concentration by comparison with calibration samples. Concentration profiles approaching pseudosteady state showed gradients from the implant toward the retinal surface, suggesting that diffusion was occurring into the retinal-choroidal-scleral (RCS) membrane. Gd-DTPA concentration varied from high values near the implant to lower values distal to the implant. Such regional concentration differences throughout the vitreous may have clinical significance when attempting to treat ubiquitous eye diseases using a single positional implant. We developed a finite element mathematical model of the rabbit eye and compared the MRI experimental concentration data with simulation concentration profiles. The model utilized a diffusion coefficient of Gd-DTPA in the vitreous of 2.8 x 10(-6) cm2 s(-1) and yielded a diffusion coefficient for Gd-DTPA through the simulated composite posterior membrane (representing the retina-choroidsclera membrane) of 6.0 x 10(-8) cm2 s(-1). Since the model membrane was 0.03-cm thick, this resulted in an effective membrane permeability of 2.0 x 10(-6) cm s(-1). Convective movement of Gd-DTPA was shown to have minimal effect on the concentration profiles since the Peclet number was 0.09 for this system.

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Section: Discussionmentioning

confidence: 99%

Study of Ocular Transport of Drugs Released from an Intravitreal Implant Using Magnetic Resonance Imaging

et al. 2005

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“…In order to cover a large number of drugs with a wide range of physicochemical properties, retinal permeabilities between 1 x 10"7 cm/s and 1 x 10"4 cm/s were considered in this study. Retinal permeabilities have been estimated for only a small number of compounds, including fluorescein (2.6 x 10"s cm/s), fluorescein glucuronide (4.5 x 10"7 cm/s), and dexamethasone sodium m-sulfobenzoate (4.9 x 10s cm/s) [13,[16][17][18][19][20]. All of the reported values fall within the range of permeabilities selected for this study.…”

Section: Model Development and Simulationsmentioning

confidence: 99%

Drug Distribution in the Vitreous Humor of the Human Eye: The Effects of Aphakia and Changes in Retinal Permeability and Vitreous Diffusivity

Friedrich¹,

Saville²,

Cheng³

1997

Journal of Ocular Pharmacology and Therapeutics

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The majority of eyes that receive drug therapy exhibit some form of pathophysiological degradation. Two common pathophysiological states are retinal inflammation, which results in breakdown of the blood-retinal barrier, and aphakia. The purpose of this study was to examine the effects of aphakia and changes in retinal permeability and vitreous diffusivity on drug distribution in the vitreous humor of the human eye. The study was performed using a finite element model that accurately accounts for the vitreous geometry and boundary conditions. Intravitreal injection is the most common method for treating posterior segment disorders; therefore, this administration method was simulated using the models. Elimination from aphakic and phakic eyes was compared for four extreme injection locations and for two retinal permeabilities. When the retinal permeability was fixed at 5.0 x 10(-5) cm/s, increasing the drug diffusivity through the vitreous from 5.4 to 10(-7) to 2.4 x 10(-5) cm2/s decreased the half-life of drug from 64 hours to 2.7 hours. When the drug diffusivity was fixed at 5.6 x 10(-6) cm2/s, increasing the retinal permeability of the drug from 1.0 x 10(-7) to 1.0 x 10(-4) cm/s decreased the half-life of drug from 44 to 7 hours. Therefore, drug diffusivity and retinal permeability are key factors that influence elimination from the vitreous, and must be considered, particularly if the blood retinal barrier has been compromised. Faster drug elimination was observed in aphakic eyes than in phakic eyes, especially for drugs with a low retinal permeability and injected close to the lens capsule. Injection position is also important if the drug is injected in close proximity to a primary elimination barrier.

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“…His group established the relationship that high molecular weight (MW) compounds have a high aqueous/vitreous ratio indicating the elimination of compounds by way of the anterior chamber. Also, there were few reports aimed at understanding spatial-temporal distribution of drug in the vitreous using mathematical modeling and computer simulations (20)(21)(22)(23)(24)(25). These studies aimed at simulating the diffusion and distribution of the drug in the vitreous humor after intravitreal injection.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Vitreal Half-Life Based on Drug Physicochemical Properties: Quantitative Structure–Pharmacokinetic Relationships (QSPKR)

et al. 2008

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In Vivo/in Vitro Correlation of Intravitreal Delivery of Drugs with the Help of Computer Simulation.

Cited by 48 publications

References 1 publication

Study of Ocular Transport of Drugs Released from an Intravitreal Implant Using Magnetic Resonance Imaging

Study of Ocular Transport of Drugs Released from an Intravitreal Implant Using Magnetic Resonance Imaging

Drug Distribution in the Vitreous Humor of the Human Eye: The Effects of Aphakia and Changes in Retinal Permeability and Vitreous Diffusivity

Prediction of Vitreal Half-Life Based on Drug Physicochemical Properties: Quantitative Structure–Pharmacokinetic Relationships (QSPKR)

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