Impact of environmental and genetic factors on codeine analgesia.

Article Details

Citation

Desmeules J, Gascon MP, Dayer P, Magistris M

Impact of environmental and genetic factors on codeine analgesia.

Eur J Clin Pharmacol. 1991;41(1):23-6.

PubMed ID
1782973 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Pharmaco-genomics
DrugInteracting Gene/EnzymeAllele nameGenotypesDefining change(s)Type(s)DescriptionDetails
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*4(A;A)Effect Directly StudiedPatients with this genotype have reduced metabolism of codeine.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*6(-;-)Effect Directly StudiedPatients with this genotype have reduced metabolism of codeine.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*5Not Available
  • Whole gene deletion, homozygote
Effect Directly StudiedPatients with this genotype have reduced metabolism of codeine.Details