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CYP2D6 genotype

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CYP2D6 genotype can help to predict effectiveness and safety during opioid treatment for chronic low back pain:

RESULTS FROM A RETROSPECTIVE STUDY IN AN ITALIAN COHORT

15 Nov 2018

C. Dagostino et al.

Pharmacogenomics and Personalized Medicine

CLBP

A retrospective analysis of a cohort to determine if CYP2D6 alleles can influence patients response in CLBP opioids therapy

Opioids

CYP2D6

Cronic Low Back Pain (CLBP)

A nonspecific form of discomfort and/or pain, localized in the low back area. It’s not attributed to a recognizable pathology, and it's often treated with painkillers

The opioids:

Patients were prescribed with:

  • Codeine and acetaminophen: is a prodrug, converted in morphin by CYP 2D6
  • Oxycodone (in some cases with naloxone): is an active drug, metabolized in the liver by CYP 2D6 in a 3-5 time more active metabolite (and partially by CYP 3A4)

The opioids:

Patients were prescribed with:

  • Codeine and acetaminophen: is a prodrug, converted in morphin by CYP 2D6
  • Oxycodone (in some cases with naloxone): is an active drug, metabolized in the liver by CYP 2D6 in a 3-5 time more active metabolite (and partially by CYP 3A4)

Stratification of patients

"CASE"

"CONTROL"

Patients showing side effects (that prejudice the treatment continuation) and no pain relief from the opioid treatment

Patients who reported pain relief with opioid treatment without side effects

Evaluation of correlation between CYP2D6 and the drugs

  • 30% or more reduction in pain (according to Brief Pain Inventory) ⇒ the treatment was considered effective
  • Severe side effects (nausea, vomiting, dizziness) were registered; some patients suspendend the treatment because of them
  • Were excluded patients with possible DDI.
  • The cohort was composed by 224 italian patients, 78 m and 146 f, with an average age of 67 years
  • Only 27 of 224 patients were in the "case" group ⇒ the sample size was extremely small
  • CYP2D6 genotyping was performed using the xTAG® CYP2D6 Kit v3 (Luminex), from germline DNA.

CYP2D6 metabolizing phenotype

Patient were stratified according to the phenotype of their enzymes too.

Results:

After the sequencing and phenotyping, emerged that:

  • *6 and *9 seems related to lack of efficiency, while *2N with the ADRs
  • *1/*11, *2N/*41 and *4/*6 instead are the most represented in the Case group
  • EM, IM and PM had similar frequencies in Case and Control

Bibliography:

  • CYP2D6 genotype can help to predict effectiveness and safety during opioid treatment for chronic low back pain: results from a retrospective study in an Italian cohort, C. Dagostino et al
  • Low Back Pain (Chronic) [Am Fam Physician. 2011;84(4):437-438], R. Chou
  • Chronic low back pain: definition and treatment [La revue du praticien, 2008 Feb 15;58(3):265-72], S. Rozenberg
  • Low back pain--from definition to diagnosis [Reumatizam, 2011;58(2):105-7], TS. Vrbanić
  • Chronic Low Back Pain on Physiopedia
  • KEGG, PGKB and wikipedia entries and data for Codeine and Oxycodone
  • xTAG® CYP2D6 Kit v3 by Luminex guide: