乌鸦传媒

LAS VEGAS -- Chronic pain patients who require high-dose opioids seem to have genetic anomalies that impact their ability to metabolize drugs, researchers reported here.

In a small survey, 91% of patients taking opioids in excess of 100 morphine milligram equivalent (MME) per day had defects in cytochrome P450 enzymes, which are involved in drug metabolism, reported , of Veract Intractable Pain Clinic in West Covina, Calif., in a poster at Pain Week.

At a separate oral presentation, Tennant said he has been working in this area of research since the 1970s, but there wasn't much interest back then.

"Now everybody's interested, because CDC regulations and state guidelines have established standard of care," said Tennant. "Every pain practitioner, if they're going to go [with a dose above 100 MME level should probably have their patients take genetic tests. This is a simple screen that is being offered by all genetic testing companies."

Tennant examined 101 chronic pain patients who required over 100 MME per day to manage their pain. Overall, 96% of these patients had anywhere between one and three defects in CYP450, with more than a quarter of those with two to three genetic defects. There were 8% of patients with defects in all three CYP450 enzymes (2D6, 2C9, and 2C19).

He also looked at a subset of 45 patients and tested for opioid receptor mu 1 (OPRM 1), which plays an important role in drug dependence, as well as Catechol-O-methyltransferase (COMT) activity, which plays a role in drug absorption. There were 28.9% of patients with intermediate or low OPRM 1 activity and 62.2% with intermediate or high COMT activity levels, both of which would be considered "defective" activity levels, and thus indicators for patients needing higher doses of opioids to control their pain.

, of Kaiser Permanente in Santa Rosa, Calif., told 乌鸦传媒 via e-mail that while opioids are one of the most potent analgesics available, clinicians know relatively little about how these drugs behave pharmacodynamically in their patients.

"Genetic testing may allow us greater insight in to how these drugs behave in the bodies of individual patients, and may be able to explain why a subset of patients seem to require very high doses," said Rubinstein, who was not involved with the research. "Exploiting genetic difference between patients may someday soon help us better target therapy so as to minimize risk to the patient while affording them optimal analgesia."

Tennant added that having a patient on such a high dose should be a reasonable indication to an insurance company or Medicare/Medicaid for a patient to receive this type of genetic test, and doctors need to "circle the wagons" to let the payers know this.

"These genetic tests arrived on the scene kind of unexpectedly, and so we're finally getting our act together in using them," said Tennant. "CMS says 'Give us an indication to pay for an expensive test.' And I think we've got an indication that should be used."

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