QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: dmd.106.010058v1 34/10/1764    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Godin, S. J. Articles by Ross, M. K. Search for Related Content PubMed PubMed Citation Articles by Godin, S. J. Articles by Ross, M. K.

Species Differences in the in Vitro Metabolism of Deltamethrin and Esfenvalerate: Differential Oxidative and Hydrolytic Metabolism by Humans and Rats

United States Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Experimental Toxicology Division, Pharmacokinetics Branch, Research Triangle Park, North Carolina (E.J.S., M.F.H., M.J.D.); Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (S.J.G.); Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee (P.M.P.); and Center for Environmental Heath Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi (M.K.R.)

Pyrethroids are neurotoxic pesticides whose pharmacokinetic behavior plays a role in their potency. This study examined the elimination of esfenvalerate and deltamethrin from rat and human liver microsomes. A parent depletion approach in the presence and absence of NADPH was used to assess species differences in biotransformation pathways, rates of elimination, and intrinsic hepatic clearance. Esfenvalerate was eliminated primarily via NADPH-dependent oxidative metabolism in both rat and human liver microsomes. The intrinsic hepatic clearance (CL_INT) of esfenvalerate was estimated to be 3-fold greater in rodents than in humans on a per kilogram body weight basis. Deltamethrin was also eliminated primarily via NADPH-dependent oxidative metabolism in rat liver microsomes; however, in human liver microsomes, deltamethrin was eliminated almost entirely via NADPH-independent hydrolytic metabolism. The CL_INT for deltamethrin was estimated to be 2-fold more rapid in humans than in rats on a per kilogram body weight basis. Metabolism by purified rat and human carboxylesterases (CEs) were used to further examine the species differences in hydrolysis of deltamethrin and esfenvalerate. Results of CE metabolism revealed that human carboxylesterase 1 (hCE-1) was markedly more active toward deltamethrin than the class 1 rat CEs hydrolase A and B and the class 2 human CE (hCE-2); however, hydrolase A metabolized esfenvalerate 2-fold faster than hCE-1, whereas hydrolase B and hCE-1 hydrolyzed esfenvalerate at equal rates. These studies demonstrate a significant species difference in the in vitro pathways of biotransformation of deltamethrin in rat and human liver microsomes, which is due in part to differences in the intrinsic activities of rat and human carboxylestersases.

This article has been cited by other articles:

				E. J. Scollon, J. M. Starr, S. J. Godin, M. J. DeVito, and M. F. Hughes In Vitro Metabolism of Pyrethroid Pesticides by Rat and Human Hepatic Microsomes and Cytochrome P450 Isoforms Drug Metab. Dispos., January 1, 2009; 37(1): 221 - 228. [Abstract] [Full Text] [PDF]

				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]