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https://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. |
DOI: | 10.1016/S0014-2999(01)01185-2 |
Description (link): | http://www.elsevier.com/wps/find/journaldescription.cws_home/506087/description#description |
Published version: | http://dx.doi.org/10.1016/s0014-2999(01)01185-2 |
Appears in Collections: | Aurora harvest 2 Pharmacology publications |
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