Abstract
Purpose: The aim of our present work is the development of a quasi steady-state model for the distribution of intravitreally injected drugs and investigation of the effects of various model parameters on the drug distribution in normal and diseased eyes. Method: A simple mathematical model for the intravitreal transport of drugs was developed using Fick's law of diffusion, Darcy's law of convective flow, and Michaelis –Menten kinetics of metabolism. A Crank- Nicolson finite difference scheme of the equation describing the drug transport in the vitreous body was written, in which the radial and axial diffusive terms and convective terms of the equation were approximated by central differences, while the temporal terms were approximated by average of forward and backward time differences. A system of linear algebraic equations obtained from the Crank Nicolson finite difference scheme was solved by line Jacobi iterative scheme in which successive improved approximate results are obtained. Result: The model predicts that an increase in the metabolic (consumption) rate and drug release rate constant reduces the concentration of intravitreally injected drug at the centre of retina and along centreline of vitreous body. A significant increase in the drug concentration at the centre of retina and along the centreline of the vitreous body in the eye afflicted with glaucoma and retinal detachment is observed and the decay rate of drug concentration in these pathological states is higher than that in the normal eyes. Conclusion: The vitreous outflow as observed in the glaucomatous and/- or rhegmatogenous eyes may contribute to the transport of intravitreally injected drug in the vitreous body. The drug concentration in the vitreous body and at the centre of retina in such diseased eyes is higher than that in the normal eyes and the decay rate of drug concentration is significantly enhanced. Keywords: Convective-diffusive transport, intravitreal injection, line-Jacobi iterative technique, release rate.Tropical Journal of Pharmaceutical Research Vol. 7 (1) 2008: pp. 867-877
Highlights
Trop J Pharm Res, March 2008; 7 (1). Several vitroretinal diseases such as cytomegalovirus retinitis, age- related macular degeneration (AMD), retinitis pigmentosa (R.P), diabetic retinopathy and a combination of similar retinal diseases are currently being treated by using drug intravitreal injection or control release implant of drugs[1]
It is observed from curves that the drug concentration increases with time in initial hours after intravitreal injection
The concentration distribution of intravitreally injected drug and the change in drug concentration with time at the centre of retina are relevant for treatment of some vitro-retinal diseases such as, age-related macular degeneration (AMD), retinitis pigmentosa, glaucoma, rhegmatogenous retinal detachment etc
Summary
Several vitroretinal diseases such as cytomegalovirus retinitis, age- related macular degeneration (AMD), retinitis pigmentosa (R.P), diabetic retinopathy and a combination of similar retinal diseases are currently being treated by using drug intravitreal injection or control release implant of drugs[1]. The diffusion of drug, convection of vitreous outflow, enzymatic reaction (metabolism), drug binding and efficacy of delivery system mainly control the bioavailability of drug after its intravitreal injection and controlled release implant. Et al 6 developed a mathematical model for prediction of the biodistribution of drug in the vitreous body released from injectable biodegradable polymer microspheres. They considered the diffusive and convective mass transport of drug within the vitreous and neglected the metabolic consumption and degradation of drug in vitreous body. Kakuji 11 has presented a pharmacokinetic model for ocular drug delivery in the spherical modified cylindrical eye based on Fick’s law of diffusion but neglected the convective transport
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