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In vitro metabolism study of carbofuran and its metabolic interaction with testosterone.
Usmani KA; Hodgson E; Rose RL
Drug Metab Rev 2004 Sep; 36(Suppl 1):534
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 µM) 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.
Pesticides; Pesticides-and-agricultural-chemicals; Pesticide-residues; Agricultural-chemicals; Agricultural-industry; Agriculture; In-vitro-study; Metabolic-study; Insecticides
Department of Environmental and Molecular Toxicology, Box 7633, North Carolina State University, Raleigh, NC 27695
Drug Metabolism Reviews
East Carolina University
Page last reviewed: March 3, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division