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Physiologically based pharmacokinetics (PBPK)

(2009) DRUG METABOLISM REVIEWS. 41(3). p.391-407
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Abstract
Allometric scaling is widely used to predict human pharmacokinetic parameters from preclinical species, and many different approaches have been proposed over the years to improve its predictive performance. Nevertheless, prediction errors are commonly observed in the practical application of simple allometry, for example, in cases where the hepatic metabolic clearance is mainly determined by enzyme activities, which do not scale allometrically across species. Therefore, if good correlation was noted for some drugs, poor correlation was observed for others, highlighting the need for other conceptual approaches. Physiologically based pharmacokinetic (PBPK) models are now a well-established approach to conduct extrapolations across species and to generate simulations of pharmacokinetic profiles under various physiological conditions. While conventional pharmacokinetic models are defined by drug-related data themselves, PBPK models have richer information content and integrate information from various sources, including drug-dependent, physiological, and biological parameters as they vary in between species, subjects, or with age and disease state. Therefore, the biological and mechanistic bases of PBPK models allow the extrapolation of the kinetic behavior of drugs with regard to dose, route, and species. In addition, by providing a link between tissue concentrations and toxicological or pharmacological effects, PBPK modeling represents a framework for mechanistic pharmacokinetic-pharmacodynamic models.
Keywords
Physiologically based pharmacokinetic, interspecies extrapolation, physiology, discovery, development, population, IN-VITRO DATA, PLASMA PARTITION-COEFFICIENTS, HEPATIC METABOLIC-CLEARANCE, VIVO DRUG CLEARANCE, QUANTITATIVE PREDICTION, TISSUE DISTRIBUTION, INTESTINAL-ABSORPTION, CANDIDATE SELECTION, XENOBIOTIC LEVELS, RISK-ASSESSMENT, allometry, human prediction, pharmacokinetic/pharmacodynamic

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Chicago
Espié, Pascal, Dominique Tytgat, Maria-Laura Sargentini-Maier, Italo Poggesi, and Jean-Baptiste Watelet. 2009. “Physiologically Based Pharmacokinetics (PBPK).” Drug Metabolism Reviews 41 (3): 391–407.
APA
Espié, P., Tytgat, D., Sargentini-Maier, M.-L., Poggesi, I., & Watelet, J.-B. (2009). Physiologically based pharmacokinetics (PBPK). DRUG METABOLISM REVIEWS, 41(3), 391–407.
Vancouver
1.
Espié P, Tytgat D, Sargentini-Maier M-L, Poggesi I, Watelet J-B. Physiologically based pharmacokinetics (PBPK). DRUG METABOLISM REVIEWS. 2009;41(3):391–407.
MLA
Espié, Pascal, Dominique Tytgat, Maria-Laura Sargentini-Maier, et al. “Physiologically Based Pharmacokinetics (PBPK).” DRUG METABOLISM REVIEWS 41.3 (2009): 391–407. Print.
@article{4324902,
  abstract     = {Allometric scaling is widely used to predict human pharmacokinetic parameters from preclinical species, and many different approaches have been proposed over the years to improve its predictive performance. Nevertheless, prediction errors are commonly observed in the practical application of simple allometry, for example, in cases where the hepatic metabolic clearance is mainly determined by enzyme activities, which do not scale allometrically across species. Therefore, if good correlation was noted for some drugs, poor correlation was observed for others, highlighting the need for other conceptual approaches. Physiologically based pharmacokinetic (PBPK) models are now a well-established approach to conduct extrapolations across species and to generate simulations of pharmacokinetic profiles under various physiological conditions. While conventional pharmacokinetic models are defined by drug-related data themselves, PBPK models have richer information content and integrate information from various sources, including drug-dependent, physiological, and biological parameters as they vary in between species, subjects, or with age and disease state. Therefore, the biological and mechanistic bases of PBPK models allow the extrapolation of the kinetic behavior of drugs with regard to dose, route, and species. In addition, by providing a link between tissue concentrations and toxicological or pharmacological effects, PBPK modeling represents a framework for mechanistic pharmacokinetic-pharmacodynamic models.},
  author       = {Espi{\'e}, Pascal and Tytgat, Dominique and Sargentini-Maier, Maria-Laura and Poggesi, Italo and Watelet, Jean-Baptiste},
  issn         = {0360-2532},
  journal      = {DRUG METABOLISM REVIEWS},
  keyword      = {Physiologically based pharmacokinetic,interspecies extrapolation,physiology,discovery,development,population,IN-VITRO DATA,PLASMA PARTITION-COEFFICIENTS,HEPATIC METABOLIC-CLEARANCE,VIVO DRUG CLEARANCE,QUANTITATIVE PREDICTION,TISSUE DISTRIBUTION,INTESTINAL-ABSORPTION,CANDIDATE SELECTION,XENOBIOTIC LEVELS,RISK-ASSESSMENT,allometry,human prediction,pharmacokinetic/pharmacodynamic},
  language     = {eng},
  number       = {3},
  pages        = {391--407},
  title        = {Physiologically based pharmacokinetics (PBPK)},
  url          = {http://dx.doi.org/10.1080/10837450902891360},
  volume       = {41},
  year         = {2009},
}

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