Generic Solving of One-compartment Toxicokinetic Models
Résumé
This paper gives the full analytical solution of the generic set of ordinary differential equations that define onecompartment toxicokinetic models. These models describe the uptake and elimination processes that occur within living organisms when exposed to chemical substances. The models solved in this paper consider living organisms as a unique compartment, into which a parent compound enters via several possible exposure routes and from which it is eliminated as well as its potential metabolites. Benefiting from generic solutions of onecompartment toxicokinetic models is particularly useful when fitting them to experimental data, facilitating the writing of the inference algorithms leading to parameter estimates. Additionally, these models are of crucial interest in environmental risk assessment for the calculation of bioaccumulation metrics as required by regulators in support of decision-making when they evaluate dossiers for marketing authorisation of active substances.
Mots clés
Ordinary differential equations
Environmental risk assessment
Living organisms
Active substances
Toxicokinetic models
Bioaccumulation metrics. Abbreviations: ADME
absorption
distribution
metabolism and excretion
EFSA
European food safety authority
ERA
environmental risk assessment
ODE
ordinary differential equation
PBPK
physiologically based pharmacokinetic
PBTK
physiologically based toxicokinetic
TK
toxicokinetic
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Charles, Ratier, Lopes - 2021 - Journal of Exploratory Research in Pharmacology(3).pdf (3.01 Mo)
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