Pharmacodynamic models of age-structured cell populations

Verfasser / Beitragende:
[Wojciech Krzyzanski]
Ort, Verlag, Jahr:
2015
Enthalten in:
Journal of Pharmacokinetics and Pharmacodynamics, 42/5(2015-10-01), 573-589
Format:
Artikel (online)
ID: 605534128
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024 7 0 |a 10.1007/s10928-015-9446-9  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s10928-015-9446-9 
100 1 |a Krzyzanski  |D Wojciech  |u Department of Pharmaceutical Sciences, University at Buffalo, 370 Kapoor Hall, 14214, Buffalo, NY, USA  |4 aut 
245 1 0 |a Pharmacodynamic models of age-structured cell populations  |h [Elektronische Daten]  |c [Wojciech Krzyzanski] 
520 3 |a The purpose of this work is to review basic pharmacodynamic (PD) models describing drug effects on cell populations and expand them to age-structured models using the theory of physiologically structured populations. The plasma drug concentrations are interpreted as the environment affecting the cell production and mortality rates. An explicit solution to model equations provides the age density distribution that serves to establish a relationship between the cell lifespan distribution and the hazard of cell removal. Given the lifespan distributions, the age distributions for most commonly applied PD models of cell responses including basic cell turnover, transit compartments, and basic lifespan models have been derived both for the baseline conditions and drug treatment. The steady-state age distribution for basic indirect response models is exponential, and it is uniform for the basic lifespan model. As an example of more complex cell population, the age distribution of human red blood cells has been simulated based on a recent model of red blood cell survival. The age distribution for cells in the transit compartment model is the sum of the gamma functions. Means and variances of age distributions for all discussed models were calculated. A brief discussion of numerical challenges and possible future model developments is presented. 
540 |a Springer Science+Business Media New York, 2015 
690 7 |a Cell population  |2 nationallicence 
690 7 |a Age structure  |2 nationallicence 
690 7 |a Pharmacodynamic model  |2 nationallicence 
690 7 |a Mortality rate  |2 nationallicence 
690 7 |a Lifespan distribution  |2 nationallicence 
773 0 |t Journal of Pharmacokinetics and Pharmacodynamics  |d Springer US; http://www.springer-ny.com  |g 42/5(2015-10-01), 573-589  |x 1567-567X  |q 42:5<573  |1 2015  |2 42  |o 10928 
856 4 0 |u https://doi.org/10.1007/s10928-015-9446-9  |q text/html  |z Onlinezugriff via DOI 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s10928-015-9446-9  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 100  |E 1-  |a Krzyzanski  |D Wojciech  |u Department of Pharmaceutical Sciences, University at Buffalo, 370 Kapoor Hall, 14214, Buffalo, NY, USA  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Journal of Pharmacokinetics and Pharmacodynamics  |d Springer US; http://www.springer-ny.com  |g 42/5(2015-10-01), 573-589  |x 1567-567X  |q 42:5<573  |1 2015  |2 42  |o 10928