Impact of environmental and genetic factors on codeine analgesia

Article Article scientifique Article Impact of environmental and genetic factors on codeine analgesia eng 1991 author Desmeules Jules Alexandre 73542 author Gascon Marie-Paule 31202 author Dayer P author Magistris M 23-26 10.1007/BF00280101 1782973 0031-6970 The polymorphic cytochrome P-450 DB1 (P-450 IID6) is responsible for the O-demethylation of codeine to morphine by human liver microsomes. The influence of P-450 DB1 variable activity on the bioactivation of codeine in vivo to morphine and on its analgesic effect was investigated in phenotyped healthy volunteers--7 extensive [EM] and 1 poor [PM] metabolizer of debrisoquine. After pretreatment with oral placebo or quinidine sulphate 50 mg, codeine phosphate 100 mg or placebo were administered orally according to a double-blind randomized crossover design. In EM subjects the plasma morphine Cmax was 17.9 nmol/l, whereas virtually no morphine was detectable after quinidine pretreatment (1.5 nmol/l), and in the PM subject (0.60 nmol/l). In EM codeine significantly increased subjective (VAS) and objective (R-III reflex) pain thresholds in response to selective transcutaneous nerve stimulation, whereas no significant analgesia was detected after placebo, or after codeine with quinidine pretreatment, or in the PM. In PM of genetic origin, or due to environmental alteration of the phenotypic expression (i.e. drug interaction), codeine is not activated into morphine and is an inefficient analgesic. Administration, Oral Adult Biotransformation Codeine/metabolism/pharmacology Cytochrome P-450 CYP2D6 Cytochrome P-450 Enzyme System/metabolism Female Humans Male Mixed Function Oxygenases/metabolism Morphine/blood Pain Measurement/drug effects Dewey 615 Dewey 617 31 Section des sciences pharmaceutiques 17 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 false 302 Groupe Desmeules Jules (pharmacologie/toxicologie) 567 European journal of clinical pharmacology 41 1 7354a455-c09f-4b60-ac5d-5cbfa366d8e5 Article (Published version) Restricted art_10.1007_BF00280101.pdf 386331 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences

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Impact of environmental and genetic factors on codeine analgesia	European journal of clinical pharmacology			1991	434	0

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Gascon, Marie-Paule