Frequently used in the pediatric population, codeine is a narcotic analgesic in prodrug form. In the body, codeine is metabolized to morphine through the CYP2D6 pathway. In the general population, it is estimated that approximate 10% of codeine undergoes conversion to morphine.
We’re generally familiar with the concept that a certain percentage of the population is ineffective at metabolizing codeine, and therefore receives no additional analgesic effect. However, the flip side, as these authors report, is a CYP2D6 genotype of over-metabolizers. In this case series, the over-metabolism of codeine in three post-surgical children likely resulted in supra-therapeutic conversion to morphine, leading to respiratory arrest.
The short summary – when possible, avoid medications that are unpredictably metabolized – such as codeine.
“More Codeine Fatalities After Tonsillectomy in North American Children”
www.ncbi.nlm.nih.gov/pubmed/22492761
CYP2D6, I believe. Wonder how common a duplicate cyp2D6 gene is? Any idea?
Mary Shue, ED RPh
University of Michigan Health System
Aha, you found a typo! – now corrected.
Regarding the CYP2D6 variability, I have copied and pasted directly from Wikipedia:
"Ethnicity is a factor in the occurrence of CYP2D6 variability. The prevalence of CYP2D6 poor metabolizers is approximately 6–10% in white populations, but is lower in most other ethnic groups such as Asians (2%).[6] In blacks, the frequency of poor metabolizers is greater than for whites.[7] The occurrence of CYP2D6 ultrarapid metabolisers appears to be greater among Middle Eastern and North African populations.[8]
This variability is accounted for by the differences in the prevalence of various CYP2D6 alleles among the populations–approximately 10% of whites appear to have the non-functional CYP2D6*4 allele,[5] while approximately 50% of Asians possess the CYP2D6*10 allele,[5] which should produce decreased CYP2D6 function; however this still appears to be within the normal range and are still grouped as intermediate metabolisers."