Biomaterial Database

Uncertainty, variability, and sensitivity analysis in physiological pharmacokinetic models. 1995

D Krewski, and Y Wang, and S Bartlett, and K Krishnan

Health Protection Branch, Health Canada, Ottawa, Ontario, Canada.

Physiologically based pharmacokinetic (PBPK) models are now commonly used to predict the dose of toxic metabolites of chemical substances reaching target tissues. A typical PBPK model can involve 20 or more physiological, physiochemical, and biochemical parameters, each of which is estimated with some degree of error. In this article, methods for assessing the impact of uncertainty in the parameter values on prediction of tissue dose are proposed, along with methods for identifying those parameters to which predictions of tissue doses are most sensitive. Many of the model parameters are related to body weight, which is assumed to vary in accordance with a doubly truncated normal distribution. The application of the proposed methods is illustrated using a PBPK model for benzene.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009929	Organ Size	The measurement of an organ in volume, mass, or heaviness.	Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010599	Pharmacokinetics	Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology.	ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D011336	Probability	The study of chance processes or the relative frequency characterizing a chance process.	Probabilities
D011650	Pulmonary Alveoli	Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place.	Alveoli, Pulmonary,Alveolus, Pulmonary,Pulmonary Alveolus
D001835	Body Weight	The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	Body Weights,Weight, Body,Weights, Body
D002302	Cardiac Output	The volume of BLOOD passing through the HEART per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with STROKE VOLUME (volume per beat).	Cardiac Outputs,Output, Cardiac,Outputs, Cardiac
D002627	Chemistry, Physical	The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes.	Physical Chemistry,Chemistries, Physical,Physical Chemistries
D003198	Computer Simulation	Computer-based representation of physical systems and phenomena such as chemical processes.	Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer