Abstract
Age-structured cell population model was introduced to describe cell survival. The impact of the environment on the cell population is represented by drug plasma concentration. A key model variable is the hazard of cell removal that is a subject to the environment effect. The model is capable of describing cohort and random labeling cell survival data. In addition, it accounts for cell loss due to labeling of cell sample, but it lacks ability to describe the effect of label elution on the survival data. The model was applied to red blood cell (RBC) survival data in two groups of Wistar rats obtained by two techniques: cohort labeling using 14C-glycine (N = 4) and random labeling using biotin (N = 8). The Weibull probability density function was selected for the RBC lifespan distribution. The data were simultaneously fitted by the mixed effects model implemented in Monolix 4.3.3. The estimated typical values of RBC lifespan and age were 53.7 and 27.8 days, respectively. A noticeable effect of biotinylation on RBC survival was observed that resulted in a significant difference between the means of individual RBC lifespan for two groups. The model provides a mechanistic framework flexible enough to account for various experimental designs to generate the cell survival data. Despite model qualification using animal data, the model has the same potential to be applied to cell survival data analysis in humans.
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Acknowledgements
Authors are thankful to Dr. Michael Garrick from University at Buffalo for his help with implementing the 14C-glycine labeling protocol into the cohort RBC labeling study.
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Krzyzanski, W., Wiczling, P. & Gebre, A. Age-structured population model of cell survival. J Pharmacokinet Pharmacodyn 44, 305–316 (2017). https://doi.org/10.1007/s10928-017-9520-6
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DOI: https://doi.org/10.1007/s10928-017-9520-6