ToxSci Advance Access published online on July 10, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl056
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 College of Public Health, Department of Environmental Health Science, University of Georgia, Athens, GA 30602-2102
* To whom correspondence should be addressed. Deltamethrin (DLT) is a Type II pyrethroid insecticide widely used in agriculture and public health. DLT is a potent neurotoxin that is primarily cleared from the body by metabolism. To better understand the dosimetry of DLT in the central nervous system, a physiologically based pharmacokinetic (PBPK) model for DLT was constructed for the adult, male Sprague-Dawley (SD) rat that employed both flow-limited (brain, GI tract, liver and rapid-perfused tissues) and diffusion-limited (fat, blood/plasma and slowly-perfused tissues) rate equations. The blood was divided into plasma and erythrocytes. Cytochrome P450-mediated metabolism was accounted for in the liver and carboxylesterase-mediated metabolism in plasma and liver. Serial blood, brain and fat samples were taken for DLT analysis for up to 48 h after adult rats received 2 or 10 mg DLT/kg po. Hepatic biotransformation accounted for 75 - 83% of these administered doses. Plasma carboxylesterases accounted for biotransformation of
Received February 20, 2006
Accepted June 29, 2006
Risk Assessment
Development of a Physiologically Based Pharmacokinetic Model for Deltamethrin in the Adult Male Sprague-Dawley Rat
Ahmad Mirfazaelian 1,
Kyu-Bong Kim 2,
Sathanandam S. Anand 3,
Hyo J. Kim 3,
Rogelio Tornero-Velez 4,
James V. Bruckner 3,
and
Jeffrey W. Fisher 1 *
2 Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2354; Pharmacology Department, National Institute of Toxicological Research, Korea Food and Drug Administration, 5-Nokbun-dong, Eunpyung-gu, Seoul 122-704, South Korea
3 Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-2354
4 U.S. Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, Research Triangle Park, NC, USA
Jeffrey W. Fisher, E-mail: jwfisher{at}uga.edu
Abstract 
8% each dosage. Refined PBPK model forecasts compared favorably to the 2 and 10 mg/kg po blood, plasma, brain and fat DLT profiles, as well as profiles subsequently obtained from adults rats given 1 mg/kg iv. DLT kinetic profiles extracted from published reports of oral and iv experiments were also used for verification of the model's simulations. There was generally good agreement in most instances between predicted and the limited amount of empirical data. It became clear from our modeling efforts that there is considerably more to be learned about processes that govern GI absorption and exsorption, transport, binding, brain uptake and egress, fat deposition, and systemic elimination of DLT and other pyrethroids. The current model can serve as a foundation for construction of models for other pyrethroids, and can be improved as more definitive information on DLT kinetic processes becomes available.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K.-B. Kim, S. S. Anand, H. J. Kim, C. A. White, and J. V. Bruckner Toxicokinetics and Tissue Distribution of Deltamethrin in Adult Sprague Dawley Rats Toxicol. Sci., February 1, 2008; 101(2): 197 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Godin, J. A. Crow, E. J. Scollon, M. F. Hughes, M. J. DeVito, and M. K. Ross Identification of Rat and Human Cytochrome P450 Isoforms and a Rat Serum Esterase That Metabolize the Pyrethroid Insecticides Deltamethrin and Esfenvalerate Drug Metab. Dispos., September 1, 2007; 35(9): 1664 - 1671. [Abstract] [Full Text] [PDF]
|
|