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Development of a Physiologically Based Pharmacokinetic Model for Triadimefon and Triadimenol in Rats and Humans
Citation:
Crowell, S. R., W. M. HENDERSON, J. F. KENNEKE, AND J. Fisher. Development of a Physiologically Based Pharmacokinetic Model for Triadimefon and Triadimenol in Rats and Humans. Presented at Society of Toxicology Annual Meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
Scientific meeting presentation.
Description:
A physiologically based pharmacokinetic (PBPK) model was developed for the conazole fungicide triadimefon and its primary metabolite, triadimenol. Rat tissue:blood partition coefficients and metabolic constants were measured in vitro for both compounds. Kinetic time course data for parent and metabolite were collected from several tissues after intravenous administration of triadimefon to male Sprague Dawley rats. The model adequately simulated peak blood and tissue concentrations but failed to predict the observed slow terminal clearance of both triadimefon and triadimenol from blood and tissues. Low capacity protein binding of parent and metabolite in blood and tissues was speculated as a possible explanation of clearance patterns, and model predictions were significantly improved by the addition of optimized binding parameters.
URLs/Downloads:
KENNEKE 09 127 ABSTRACT SOT 2010.PDF (PDF, NA pp, 9 KB, about PDF)KENNEKE 09 127 POSTER SOT 2010.PDF (PDF, NA pp, 759 KB, about PDF)