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In vitro metabolism study of carbofuran and its metabolic interaction with testosterone.

Authors
Usmani-KA; Hodgson-E; Rose-RL
Source
Drug Metab Rev 2004 Sep; 36(Suppl 1):534
NIOSHTIC No.
20026148
Abstract
Carbofuran is a widely used carbamate pesticide in agricultural practice throughout the world. Its effect as a pesticide is due to its ability to inhibit acetylcholinesterase activity. This study was designed to investigate the in vitro human and rodent metabolism of carbofuran, human cytochrome P450 (CYP) isoforms, and possible interactions with testosterone. Carbofuran is metabolized by CYPs leading to the production of a major ring oxidation metabolite, 3-hydroxycarbofuran, and two minor metabolites. Pooled HLM have a significantly higher Km value (1950 ÁM) than RLM Km (210 microM) and MLM Km (550 microM) and intrinsic clearance rate calculations indicate that HLM metabolize carbofuran to 3-hydroxycarbofuran almost 14-folds lower than RLM and MLM. Differences between rat and human are due to rat CYP2Cs. Among 16 human cDNA-expressed CYP enzymes examined, CYP3A4 was the major isoform responsible for carbofuran metabolism to 3-hydroxycarbofuran. Use of phenotyped HLM demonstrated that the variation in carbofuran metabolism among 17 single-donor HLM samples is over 5-fold and the best correlation between CYP isoform activity and carbofuran metabolism was observed with CYP3A4. The interaction of carbofuran with an endogenous CYP3A4 substrate, testosterone (TST), was investigated. TST metabolism was activated by carbofuran in HLM and CYP3A4, however, less activation was observed for carbofuran metabolism by TST in HLM and CYP3A4.
Keywords
Pesticides; Pesticides-and-agricultural-chemicals; Pesticide-residues; Agricultural-chemicals; Agricultural-industry; Agriculture; In-vitro-study; Metabolic-study; Insecticides
Contact
Department of Environmental and Molecular Toxicology, Box 7633, North Carolina State University, Raleigh, NC 27695
CODEN
DMTRAR
CAS No.
1563-66-2
Publication Date
20040901
Document Type
Abstract
Funding Type
Cooperative Agreement
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Identifying No.
Cooperative-Agreement-Number-U50-OH-007551
ISSN
0360-2532
Source Name
Drug Metabolism Reviews
State
NC
Performing Organization
East Carolina University
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