Genetic Makeup May Help Explain Methadone Overdoses

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Researchers say they’ve identified genetic variations that affect how quickly people metabolize the synthetic drug methadone.

Methadone is used to treat pain or addiction to powerful narcotic pain drugs and heroin. However, methadone can be deadly if it remains in the body too long.

“A person’s genetic makeup influences how an enzyme in the liver metabolizes methadone,” said principal investigator Dr. Evan Kharasch, professor of biochemistry and molecular biophysics at Washington University School of Medicine in St. Louis.

“This explains why some people can have very high levels of methadone in their blood — high enough to trigger a potential overdose — even if they have received the same dose of the drug as others who are not affected the same way,” he said in a university news release.

It was known that people metabolize methadone differently, but it was not completely understood how a person’s genetic makeup affected that process.

The researchers said they pinpointed genetic subtypes that affect methadone metabolism. They said if genetic testing is used before patients are prescribed methadone, the new findings could help prevent some of the 5,000 deaths due to methadone overdoses that occur each year in the United States.

The study team analyzed blood samples from healthy volunteers to determine their genetic makeup, and then gave them methadone to see how rapidly it cleared from their bodies. The results showed that variations in a gene that influences methadone clearance in the liver had a major effect on how long the drug stayed in the body.

Blacks were more likely than whites to have higher methadone levels in the blood despite receiving equal amounts of the drug, the study found. Blacks also were more likely to have the gene variant associated with slower methadone metabolism and less likely to have the gene variant associated with faster methadone metabolism, the researchers said.

“We think that may explain why African-Americans and Caucasian patients typically clear methadone at different rates,” Kharasch said.

The researchers also found that the genetic variants were more likely to affect metabolism of methadone in liquid or pill form than intravenous methadone. That finding is important because primary care doctors are more likely to prescribe the oral form and may not be as familiar with the difficulties in using methadone to treat pain as pain management specialists, the investigators said.

The study was published online recently in the journal Anesthesiology.

More information

The U.S. National Library of Medicine has more about methadone.

Source: HealthDay

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