| Physiologically based pharmacokinetic modeling of deltamethrin: development of a rat and human diffusion-limited model. | |
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MedLine Citation:
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PMID: 20200215 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mirfazaelian et al. developed a physiologically based pharmacokinetic (PBPK) model for the pyrethroid pesticide deltamethrin in the rat. This model describes gastrointestinal (GI) tract absorption as a saturable process mediated by phase III efflux transporters which pump deltamethrin out of the intestinal enterocytes into the GI tract lumen, resulting in minimal net absorption at low concentrations and increasing absorption at higher concentrations. In the present study, the dose dependency in absorption of deltamethrin was examined in male Long Evans rats using po exposures predicted by the Mirfazaelian model to yield different po bioavailability values. No difference in the bioavailability from single po doses of 0.3 and 3.0 mg/kg deltamethrin was observed. Based on this finding, the Mirfazaelian PBPK model was modified to exclude a saturable absorption process. Other changes to the Mirfazaelian model included describing all tissue compartments with diffusion-limited kinetics and a single blood compartment. These changes improved model predictions of deltamethrin tissue concentration data from the present study and the literature. The rat model was then scaled to humans. The model predicted a twofold greater peak deltamethrin brain concentration and threefold greater area under the curve (AUC(0-48 h)) for humans following an po exposure of 1 mg/kg. Based on this model, humans would have greater distribution of deltamethrin to the brain for the same administered po dose compared to rats. The relative sensitivity to deltamethrin between rats and humans depends on both pharmacokinetic and pharmacodynamic differences. Species differences in the pharmacodynamic responses to deltamethrin between rats and humans remain uncharacterized. |
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Authors:
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Stephen J Godin; Michael J DeVito; Michael F Hughes; David G Ross; Edward J Scollon; James M Starr; R Woodrow Setzer; Rory B Conolly; Rogelio Tornero-Velez |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-03-03 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: 115 ISSN: 1096-0929 ISO Abbreviation: Toxicol. Sci. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-18 Completed Date: 2010-08-10 Revised Date: 2010-09-17 |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: United States |
Other Details:
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Languages: eng Pagination: 330-43 Citation Subset: IM |
Affiliation:
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Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Animals Dose-Response Relationship, Drug Enterocytes / drug effects, metabolism Humans Insecticides / pharmacokinetics* Intestinal Absorption / drug effects, physiology Male Models, Biological Nitriles / pharmacokinetics* Pyrethrins / pharmacokinetics* Rats Rats, Long-Evans Species Specificity |
| Chemical | |
Reg. No./Substance:
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0/Insecticides; 0/Nitriles; 0/Pyrethrins; 52820-00-5/decamethrin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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