Cytochrome P450 Defects Linked to Opioid Regimen Efficacy

A recent study suggests that most patients with multiple defects of the cytochrome P450 system naturally gravitated toward an opioid regimen primarily metabolized through the cytochrome P450 (CYP450) 3A4 enzyme or a non-cytochrome, as presented at the 30th Annual Meeting of the American Academy of Pain Medicine.

Patients were initially referred for intractable pain therapy that had not responded to standard low doses of opioids. Study authors emphasized that “non-responsive” or “resistant” patients need CYP450 testing since their multiple metabolic defects allow them to only respond to some opioids. Certain patients eliminate drugs quickly or more slowly based on the action of metabolizing enzymes. This further affects the drug’s efficacy or toxicity.

A total of 49 patients were assayed for CYP450, 2D6, 2C9, and 2C19 with 2 or 3 cytochrome defects that might affect metabolism. A defect was defined by any sign of a poor, rapid or intermediate metabolizer, whereas an extensive metabolizer was considered normal. Researchers found that 1 or more of the following opioids provided sufficient pain control to allow daily activities and maintenance of normal blood pressure and pulse rate:

Fentanyl in 18 (30.7%) and oxycodone in 26 (53.1%) patients; Fentanyl and oxycodone are metabolized primarily through the CYP3A4 enzyme
Morphine in 24 (49.0%) and hydromorphone in 26 (53.1%) patients; both drugs are metabolized by Phase 2 glucuronidation
Hydrocodone in 5 (10.2%) and methadone in 9 (18.4%) of patients; hydrocodone is metabolized by the CYP2D6 enzyme, while the methadone is metabolized by as many as 6 different enzymes
Seven (14.3%) patients required injectable opioids because they did not respond to oral opioids, perhaps due to the large number of cytochrome P450 enzymes present in the intestine and liver

Study results suggest patients showed a propensity to opioid response using metabolic pathways consistent with prior test results indicating CYP450 function. This may help future considerations in choosing the optimal opioid regimen when indicated for intractable pain.

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