PMID: 8998950May 1, 1996Paper

Incorporating Monte Carlo simulation into physiologically based pharmacokinetic models using advanced continuous simulation language (ACSL): a computational method

Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology
R S ThomasR S Yang

Abstract

Biologically based models with physiological parameters are becoming more popular as a tool to estimate target tissue doses from chemical exposures. However, the majority of current physiologically based pharmacokinetic (PBPK) models do not take into account the uncertainty and/or variability within the various model parameters. Consideration of uncertainty is important to evaluate the predictive ability and complexity of a model as well as identification of parameters which contribute disproportionately to variability in model output. In order to estimate the uncertainty in PBPK model output, a versatile and simple computational method is presented which can be readily incorporated into the majority of PBPK models without extensive additions to model computer code. In this paper, a separate computer program for Monte Carlo simulation is furnished that randomly samples values for model parameters and writes them into a run-time language (command file) format which can then be utilized to execute individual PBPK models. Modifications to the PBPK model allow the desired output to be written to a data file for statistical analysis. The method presented in this paper is applied to a simple PBPK model for benzene disposition.

Citations

Mar 29, 2003·Regulatory Toxicology and Pharmacology : RTP·G M PastinoE J Flynn
Mar 27, 2010·Journal of Veterinary Internal Medicine·D L Gustafson, D H Thamm
Jul 13, 2002·Journal of Pharmaceutical Sciences·Daniel L GustafsonMichael E Long
Dec 4, 2003·Risk Analysis : an Official Publication of the Society for Risk Analysis·Michael PelekisJoseph S Gauthier
Jan 31, 2006·Regulatory Toxicology and Pharmacology : RTP·Dale J MarinoDavid A Morgott
Nov 9, 2000·Regulatory Toxicology and Pharmacology : RTP·J I DelicG D Loizou
May 1, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Yuching YangHarvey J Clewell
Mar 9, 2002·Toxicology and Applied Pharmacology·Fredrik Jonsson, Gunnar Johanson
Feb 28, 2017·Regulatory Toxicology and Pharmacology : RTP·Torka S PoetPaul S Price
Dec 2, 2011·Journal of Toxicology and Environmental Health. Part a·Dale J Marino
Nov 3, 2012·Journal of Toxicology and Environmental Health. Part a·Dale J Marino
Nov 9, 2011·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·F YangZ L Zeng
May 19, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Pankajini MallickMarjory Moreau
Jun 28, 2008·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Chad M ThompsonKannan Krishnan
Jun 9, 2005·Toxicology and Industrial Health·James E DennisonMelvin E Andersen
Jul 30, 2003·Clinical Pharmacokinetics·Ivan Nestorov
Feb 9, 2006·Journal of Occupational and Environmental Hygiene·Ginette TruchonGuillaume Pierrehumbert
Oct 9, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Pankajini MallickMiyoung Yoon
Feb 15, 2007·Journal of Applied Toxicology : JAT·Weihsueh A ChiuKannan Krishnan
Sep 27, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Elaina M KenyonRonald N Hines
Jun 1, 2021·Expert Opinion on Drug Metabolism & Toxicology·Miyuki BreenJohn F Wambaugh

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.