DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

0090-9556/04/3208-786-793$20.00
DMD 32:786-793, 2004

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Williams, M. L.
Right arrow Articles by Wainer, I. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Williams, M. L.
Right arrow Articles by Wainer, I. W.

EFFECTS OF PROTEIN CALORIE MALNUTRITION ON THE PHARMACOKINETICS OF KETAMINE IN RATS

Marion L. Williams, Donald E. Mager, Heli Parenteau, Girish Gudi1, Timothy S. Tracy2, Mike Mulheran, and Irving W. Wainer

National Institute on Aging, Gerontology Research Center, Baltimore, Maryland (M.L.W., D.E.M., I.W.W.); Medical Research Council Toxicology Unit, University of Leicester, Leicester, United Kingdom (M.M.); AstraZeneca Research and Development, Montreal, Quebec, Canada (H.P.); and School of Pharmacy, West Virginia University, Morgantown, West Virginia (G.G., T.S.T.)

The effect of protein calorie malnutrition (PCM) on the pharmacokinetics of ketamine (KET) enantiomers has been investigated. Six control and six PCM rats were administered 85 mg/kg racemic KET by intramuscular injection, and plasma concentrations of (S)- and (R)-KET, norketamine (NKET), and 5,6-dehydronorketamine (DNK) were measured using enantioselective gas chromatography. Pharmacokinetic profiles were analyzed using standard noncompartmental and compartmental modeling methods. The volumes of distribution were similar between control and PCM rats for (S)- and (R)-KET. However, total clearance of both KET enantiomers was decreased, resulting in an increase in systemic exposure (p < 0.05). The KET absorption rate was also increased in PCM rats. A decrease in the clearance of both NKET enantiomers led to a significant increase in exposure in PCM rats (p < 0.005), and modeling results could not exclude the possibility that PCM induced an increase in the fraction of KET following the NKET pathway, which may further contribute to this increase in exposure. An increase in exposure to DNK enantiomers was also evident in PCM animals compared with controls [p < 0.005 (DNK1); N.S. (DNK2)], which was in concordance with the decrease in apparent clearance values. These results show that PCM significantly alters the pharmacokinetics of KET and several of its metabolites.

Address correspondence to: Marion L. Williams, National Institute on Aging, National Institutes of Health, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825. E-mail: Williamsma{at}grc.nia.nih.gov




This article has been cited by other articles:


Home page
 Toxicol SciHome page
S. Y. Boctor, C. Wang, and S. A. Ferguson
Neonatal PCP Is More Potent than Ketamine at Modifying Preweaning Behaviors of Sprague-Dawley Rats
Toxicol. Sci., November 1, 2008; 106(1): 172 - 179.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2004 by the American Society for Pharmacology and Experimental Therapeutics.