What are the half-lives of ranibizumab and aflibercept (VEGF Trap-eye) in human eyes? Calculations with a mathematical model
Keywords:age-related macular degeneration, ranibizumab, bevacizumab, VEGF Trap, aflibercept, half-lives, pharmacokinetics.
AbstractThe aim of the article is to estimate the intravitreal half-lives of ranibizumab and aflibercept (VEGF Trap-eye; VTE) in human eyes. Using a published mathematical model for rabbits, the intravitreal half-lives of ranibizumab and bevacizumab were calculated and compared to empirical data. The slope coefficient within the model was changed to set the bevacizumab output equal to experimental values to meet 3 goals: firstly, to validate the model in rabbit eyes; secondly, to test the mutability of the model to monkey eyes; thirdly, to calculate the half-lives of ranibizumab and the VTE in human eyes. The half-life calculations for ranibizumab deviate from published rabbit and monkey values by only 8.3% and 4.2%. Using the experimentally determined half-life of bevacizumab in human eyes (8.25 days) to set the equation, the half-lives of ranibizumab and the VTE are calculated to be 4.75 days and 7.13 days in human eyes. The intraocular half-lives of ranibizumab and the VTE are estimated using existing published animal and human data and a mathematical model. The validity of these half-lives and binding activities, however, awaits clinical correlation.
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