Predicting the spatial and temporal drug concentration distributions in the eyes is essential for quantitative analysis of the therapeutic effect and overdose issue via different topical administration strategies. To address such needs, an experimentally validated computational fluid dynamics (CFD) based virtual human eye model with physiologically realistic multiple ophthalmic compartments was developed to study the effect of administration frequency and interval on drug concentration distributions. Timolol was selected as the topical dosing drug for the numerical investigation of how administration strategy can influence drug transport and concentration distribution over time in the human eye. Administration frequencies employed in this study are 1-4 times per day, and the administration time intervals are Δt = 900 s, 1800 s, and 3600 s. Numerical results indicate that the administration frequency can significantly affect the temporal timolol concentration distributions in the ophthalmic compartments. More administrations per day can prolong the mediations at relatively high levels in all compartments. CFD simulation results also show that shorter administration intervals can help the medication maintain a relatively higher concentration during the initial hours. Longer administration intervals can provide a more stable medication concentration during the entire dosing time. Furthermore, numerical parametric analysis in this study indicates that the elimination rate in the aqueous humor plays a dominant role in affecting the drug concentrations in multiple ophthalmic compartments. However, it still needs additional clinical data to identify how much drugs can be transported into the cardiac and/or respiratory systems via blood circulation for side effect assessment.
Keywords: Administration frequency and interval; Computational fluid dynamics (CFD); Drug diffusion and elimination; Ocular drug delivery; Therapeutic efficacy and safety.
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