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Jie Shen, Mohammad Kazemi, Mayssa Attar; Simulation of Ocular Drug Distribution Following Zero Order Release of Intravitreally Dosed Bevacizumab Using 3D Computational Fluid Dynamic Model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):228.
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To predict the steady state ocular pharmacokinetic profile of bevacizumab following intravitreal placement of a zero-order release drug device at 5 ug/day release rate in human eyes using a 3D computational fluid dynamic model.
A 3D computational fluid dynamic model was developed based on anatomy of the human eye using ANSYS Fluent. Intravitreal location of the drug device is defined as a point source 3 mm posterior to the limbus. Diffusion coefficients of 9.43×10-7 cm2/s for bevacizumab in ocular matrices were estimated using a MW of 149kD.
Based on the model output, contour plots illustrating drug distribution over time following dosing as well as concentration-time profile for various ocular tissues are generated for up to 100 days post dosing. Steady state was reached by ~40 days post dosing, consistent with ocular half-life estimated following a single intravitreal injection of bevacizumab in human. Steady state concentration in the vitreous is estimated to be in the range of 13-19 ug/mL, exceeding that maintained within one month (~ 3 ug/mL) of an intravitreal bolus injection of 1.25 mg bevacizumab in human eyes.
3D computational fluid dynamic model allowed simulation of ocular drug distribution in multiple compartments following dosing of a zero-order release drug device for bevacizumab. Simulation results corroborated with experimentally generated kinetic data in human following bolus bevacizumab intravitreal injection, and confirmed at 5 ug/day release rate therapeutically relevant drug concentration in the eye could be exceeded.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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