Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/14437
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Type: Journal article
Title: Precipitated withdrawal following codeine administration is dependent on CYP genotype
Author: Chew, M.
White, J.
Somogyi, A.
Bochner, F.
Irvine, R.
Citation: European Journal of Pharmacology, 2001; 425(3):159-164
Publisher: Elsevier Science BV
Issue Date: 2001
ISSN: 0014-2999
1879-0712
Statement of
Responsibility: 
May Chew, Jason M. White, Andrew A. Somogyi, Felix Bochner and Rodney J. Irvine
Abstract: The role of metabolic polymorphism in the development of physical dependence to codeine was assessed in cytochrome P450 2D2 (CYP2D2) deficient Dark Agouti and CYP2D2 intact Sprague-Dawley rats by assessment of the severity of naloxone precipitated withdrawal after codeine and morphine administration. Plasma morphine concentrations after codeine were significantly higher (P<0.01) in Sprague-Dawley than in Dark Agouti rats with metabolic ratios of 0.71±0.27 and 0.07±0.04, respectively. Withdrawal after codeine resulted in significantly greater hypothermia (3.5–4 °C, P<0.0001) in Sprague-Dawley animals compared to the other groups. Body weight loss was similar for all groups ranging from 6.2±0.4 to 8.2±0.6 g. When strain and treatment data were combined, a relationship between body temperature and plasma morphine concentration could be described by the inverse Hill equation (r2=0.76, EC50=556±121 ng/ml, n=2.9±1.5). These data indicate that dependence and withdrawal after codeine administration are dependent on its bioconversion to morphine.
Keywords: Codeine; Morphine; CYP2D2; opioid dependence; opioid withdrawal
Description: Copyright © 2001 Elsevier Science B.V. All rights reserved.
RMID: 0020010774
DOI: 10.1016/S0014-2999(01)01185-2
Description (link): http://www.elsevier.com/wps/find/journaldescription.cws_home/506087/description#description
Appears in Collections:Pharmacology publications

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