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Drug Metabolism and Disposition Fast Forward
First published on June 19, 2008; DOI: 10.1124/dmd.107.020271


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Received for publication December 26, 2007.
Revised June 16, 2008.
Accepted for publication June 17, 2008.

Biodistribution of radiolabeled ethanol in rodents

Andrew N Gifford 1*, Mel Pilar Espaillat 1, Samuel John Gatley 2

1 Brookhaven National Laboratory 2 Northeastern University

* Address correspondence to: E-mail: gifforda{at}bnl.gov

Abstract

The biodistribution of [1-14C]ethanol in rodents was examined to determine sites of concentration of ethanol or its metabolites that may contribute to its toxicological and pharmacokinetic characteristics. Following intravenous administration of [1-14C]ethanol in mice, radioactivity showed a widespread distribution amongst body organs. Determination of the proportion of tissue radioactivity accounted for by volatile [1-14C]ethanol versus non-volatile 14C metabolites indicated that tissue radioactivity was mostly in the form of the latter, even as early as 5 min post-injection, indicating a rapid metabolism of the radiolabeled ethanol to labeled metabolites. In a separate study, radioactivity was imaged using whole-body autoradiography following intravenous administration in rats. High levels of radioactivity were observed in the Harderian gland, preputial gland and in the pancreas at 15 and 60 min post-injection. High levels of radioactivity were also apparent at the later time point in the intestinal tract, indicating hepatobillary excretion of radiolabeled metabolites. Moderate levels of radioactivity were present in the liver, lungs, salivary glands, bone marrow and kidney cortex. In conclusion, following intravenous [14C]ethanol administration, radioactivity initially distributes widely amongst body organs but concentrates in specific tissues at subsequent time points. Especially notable in the current study was the high concentration of radioactivity accumulating in the pancreas. It is thus tempting to speculate that the well-documented high incidence of pancreatic disease in observed in human chronic alcoholism may be related to a propensity of this organ to accumulate ethanol and/or reactive ethanol metabolite.


Key words: alcohol metabolism, distribution, drug distribution





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