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|Title:||Precipitated withdrawal following codeine administration is dependent on CYP genotype|
|Citation:||European Journal of Pharmacology, 2001; 425(3):159-164|
|Publisher:||Elsevier Science BV|
|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.|
|Appears in Collections:||Pharmacology publications|
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