Effect of Retinal Permeability, Diffusivity, and Aqueous Humor Hydrodynamics on Pharmacokinetics of Drugs in the Eye

Abstract

Thus, the combined effect of variables P, D, and F are important factors that should be considered in order to determine drug dosage. This study could be used to estimate the drug distribution and elimination for (1) wide range of physicochemical properties of drugs and (2) normal and abnormally elevated vitreous flows during the diseased condition of the eye. These results could help in obtaining essential information about the treatment protocol for targeted retinal diseases while simultaneously avoiding the toxic effects of these drugs.

Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations

“…Since the intravitreal convective flow depends on pressure, it seems obvious that an increase in the intraocular pressure could change flow values in the vitreous humor. As an example, in some pathologies such as glaucoma and retinal detachment, where higher intraocular pressure values are noticed, an increase in the convection has been observed [26,29].…”

“…The impact of both diffusion and convection flow in the drug pharmacokinetics within the vitreous humor has been studied based on different experimental data and mathematical models [7,[26][27][28][29].…”

“…Convection is the process of moving a fraction of volume of the aqueous humor produced by the ciliary processes throughout the vitreous humor towards the retina [7,26,28,29]. This process takes place due to the differences in pressure and temperature between the anterior chamber and the retinal surface [7].…”

Effects of Pathological Conditions on Ocular Pharmacokinetics of Antimicrobial Drugs

“…The literature suggests that the vitreous convective flow is higher in diseased than in normal conditions. 22) Ocular pharmacokinetics may depend on the compound. Drug concentrations in the vitreous humor of inflamed eyes at 10 h after administration was equal to or lower than in the normal eye.…”

Toxicity of a Biodegradable Microneedle Implant Loaded with Methotrexate as a Sustained Release Device in Normal Rabbit Eye: A Pilot Study

“…[15][16][17][18][19][20] A well-tolerated controlled drug release device has the potential to maintain a sufficient concentration of drug in the eye for a period of time sufficient to eradicate the target disease while avoiding undesirable and toxic peak concentrations of the drug. 16,21,22 Sustained-release implants have been developed and approved by the U.S. Food and Drug Administration (FDA) for delivery of prolonged therapeutic levels of ganciclovir in patients with cytomegalovirus retinitis and the acquired immune deficiency syndrome; other devices have been developed and approved for delivery of triamcinolone acetonide in patients with severe or chronic nonmicrobial intraocular inflammation. 15,16 Our group designed a new type of biodegradable intraocular implant loaded with methotrexate for intended treatment of selected patients with PIOL.…”