Alpha 2.0
Login Register
» Articles » PMID: 7737043

Parameter Variability and the Interpretation of Physiologically Based Pharmacokinetic Modeling Results

Overview
Journal Environ Health Perspect
Date 1994 Dec 1
PMID 7737043
Citations 7
Authors
R C Spear
F Y Bois
Affiliations
Soon will be listed here.
Abstract

For the past several years we have been working with models of benzene distribution and metabolism, principally in the rat, but more recently in humans. Our biologically related objectives have been primarily to assist our laboratory-based colleagues in their quest for understanding of the mechanisms by which benzene exerts its toxic action. A secondary goal has been to develop or adapt models useful in risk assessment applications. We have also had methodological goals that relate to applications of sensitivity analysis on the one hand, but more fundamentally to the connection between experimental data and model structure and parameterization. This paper presents an overview of our work in these areas.

Citing Articles

Does the Systemic Plasma Profile Inform the Liver Profile? Analysis Using a Physiologically Based Pharmacokinetic Model and Individual Compounds.

Li R, Maurer T, Sweeney K, Barton H AAPS J. 2016; 18(3):746-56.

PMID: 26951483 PMC: 5256613. DOI: 10.1208/s12248-016-9895-0.

Heterogeneous dynamics, robustness/fragility trade-offs, and the eradication of the macroparasitic disease, lymphatic filariasis.

Michael E, Singh B BMC Med. 2016; 14:14.

PMID: 26822124 PMC: 4731922. DOI: 10.1186/s12916-016-0557-y.

Addressing human variability in next-generation human health risk assessments of environmental chemicals.

Zeise L, Bois F, Chiu W, Hattis D, Rusyn I, Guyton K Environ Health Perspect. 2012; 121(1):23-31.

PMID: 23086705 PMC: 3553440. DOI: 10.1289/ehp.1205687.

Geographic and ecologic heterogeneity in elimination thresholds for the major vector-borne helminthic disease, lymphatic filariasis.

Gambhir M, Bockarie M, Tisch D, Kazura J, Remais J, Spear R BMC Biol. 2010; 8:22.

PMID: 20236528 PMC: 2848205. DOI: 10.1186/1741-7007-8-22.

Whole body pharmacokinetic models.

Nestorov I Clin Pharmacokinet. 2003; 42(10):883-908.

PMID: 12885263 DOI: 10.2165/00003088-200342100-00002.

References
1.
Spear R, Bois F, Woodruff T, Auslander D, Parker J, Selvin S . Modeling benzene pharmacokinetics across three sets of animal data: parametric sensitivity and risk implications. Risk Anal. 1991; 11(4):641-54. DOI: 10.1111/j.1539-6924.1991.tb00653.x. View
2.
Rickert D, Baker T, Bus J, Barrow C, Irons R . Benzene disposition in the rat after exposure by inhalation. Toxicol Appl Pharmacol. 1979; 49(3):417-23. DOI: 10.1016/0041-008x(79)90441-1. View
3.
Sabourin P, Chen B, Lucier G, Birnbaum L, Fisher E, Henderson R . Effect of dose on the absorption and excretion of [14C]benzene administered orally or by inhalation in rats and mice. Toxicol Appl Pharmacol. 1987; 87(2):325-36. DOI: 10.1016/0041-008x(87)90294-8. View
4.
Sabourin P, Bechtold W, Birnbaum L, Lucier G, Henderson R . Differences in the metabolism and disposition of inhaled [3H]benzene by F344/N rats and B6C3F1 mice. Toxicol Appl Pharmacol. 1988; 94(1):128-40. DOI: 10.1016/0041-008x(88)90343-2. View
5.
Bois F, Woodruff T, Spear R . Comparison of three physiologically based pharmacokinetic models of benzene disposition. Toxicol Appl Pharmacol. 1991; 110(1):79-88. DOI: 10.1016/0041-008x(91)90291-l. View