Tuesday, 24 May 2005

This presentation is part of: ADMET Posters

Preliminary Oral Pharmacokinetics of the Potential Chemopreventive Agents Farnesol and Geraniol

Joseph G. Desiderio, Harold Newmark, and Thomas J. Cook. Rutgers, the State University of New Jersey, Piscataway, NJ

Introduction: The isoprenoids, farnesol [FOH] and geraniol [GOH], have previously demonstrated in vitro and preclinical in vivo activity as chemopreventive and chemotherapeutic agents, yet their disposition profiles have not been fully described. To this end, preliminary pharmacokinetic studies of FOH and GOH in the rat were performed. Methods: A single oral dose (1 g/kg) of either trans-, trans-[3-,14C]-farnesol ([14C]-FOH) or [3-14C]-geraniol ([14C]-GOH) was administered to male Sprague-Dawley rats. Blood was sampled over a 24-hr period, after which the animals were euthanized and tissues, total feces and urine were collected. Plasma and urine samples were analyzed by radiometric HPLC. Tissue and feces samples were dissolved or oxidized and analyzed by LSC. Results: Preliminary pharmacokinetic model analyses suggest [14C]-FOH and [14C]-GOH are rapidly absorbed after oral administration (Tmax= 34 min and 3 hrs for [14C]-GOH and [14C]-FOH, respectively). Radiometric HPLC peaks corresponding to the respective parent compounds were absent in the plasma and urine samples. The maximal amount of radioactivity appeared in the liver of rats dosed with [14C]-FOH (4.0%) and in the small intestine of rats dosed with [14C]-GOH (3.2%). The majority of the radioactivity was excreted as metabolite in the urine (12.2% and 24.4% for [14C]-FOH and [14C]-GOH, respectively). Conclusions: The absence of parent compound in the plasma samples suggests FOH and GOH are subjected to extensive first pass metabolism in the liver and/or intestine. Their extensive metabolism has important implications on the chemopreventive potentials of FOH and GOH. Acknowledgement: Financial support from McKesson Bioservices through NCI subcontract N02-CN-95016.

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