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DOI | 10.1007/s10928-015-9424-2 |
Identifiability of PBPK models with applications to dimethylarsinic acid exposure | |
Garcia, Ramon I.1; Ibrahim, Joseph G.1; Wambaugh, John F.3; Kenyon, Elaina M.2; Setzer, R. Woodrow3 | |
发表日期 | 2015-12-01 |
ISSN | 1567-567X |
卷号 | 42期号:6页码:591-609 |
英文摘要 | Any statistical model should be identifiable in order for estimates and tests using it to be meaningful. We consider statistical analysis of physiologically-based pharmacokinetic (PBPK) models in which parameters cannot be estimated precisely from available data, and discuss different types of identifiability that occur in PBPK models and give reasons why they occur. We particularly focus on how the mathematical structure of a PBPK model and lack of appropriate data can lead to statistical models in which it is impossible to estimate at least some parameters precisely. Methods are reviewed which can determine whether a purely linear PBPK model is globally identifiable. We propose a theorem which determines when identifiability at a set of finite and specific values of the mathematical PBPK model (global discete identifiability) implies identifiability of the statistical model. However, we are unable to establish conditions that imply global discrete identifiability, and conclude that the only safe approach to analysis of PBPK models involves Bayesian analysis with truncated priors. Finally, computational issues regarding posterior simulations of PBPK models are discussed. The methodology is very general and can be applied to numerous PBPK models which can be expressed as linear time-invariant systems. A real data set of a PBPK model for exposure to dimethyl arsinic acid (DMA(V)) is presented to illustrate the proposed methodology. |
英文关键词 | PBPK Models;Identifiability;Gibbs sampling;Metropolis-Hasting algorithm;Dimethyl arsinic acid |
语种 | 英语 |
WOS记录号 | WOS:000363982800001 |
来源期刊 | JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
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来源机构 | 美国环保署 |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/58744 |
作者单位 | 1.Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA; 2.US EPA, Natl Hlth & Environm Effects Lab, Res Triangle Pk, NC 27711 USA; 3.US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA |
推荐引用方式 GB/T 7714 | Garcia, Ramon I.,Ibrahim, Joseph G.,Wambaugh, John F.,et al. Identifiability of PBPK models with applications to dimethylarsinic acid exposure[J]. 美国环保署,2015,42(6):591-609. |
APA | Garcia, Ramon I.,Ibrahim, Joseph G.,Wambaugh, John F.,Kenyon, Elaina M.,&Setzer, R. Woodrow.(2015).Identifiability of PBPK models with applications to dimethylarsinic acid exposure.JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS,42(6),591-609. |
MLA | Garcia, Ramon I.,et al."Identifiability of PBPK models with applications to dimethylarsinic acid exposure".JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS 42.6(2015):591-609. |
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