September 13, 1997
by C. Wu
For centuries, people of different cultures have used opiates to relieve pain. Now, it appears that sensitivity to the opiate codeine varies with ethnic background, according to a recent study. These findings could help doctors treat pain more effectively in different individuals.
Codeine's analgesic properties stem mainly from the body's ability to metabolize it into morphine, a much more potent opiate, says Alastair J.J. Wood of Vanderbilt University School of Medicine in Nashville. His research indicates that further reactions contribute to the pain-killing response. Wood and his colleagues examined the effects of codeine in men of European extraction and in Asian men. Both groups transformed codeine into morphine similarly, but the Asian men experienced significantly weaker effects from the drug.
Wood presented the findings this week at a meeting of the American Chemical Society in Las Vegas.
"It's a nice piece of work," says Wendel L. Nelson of the University of Washington in Seattle. Researchers had suspected that morphine is responsible for the pain relief provided by codeine, but the current study "is the clinical piece that really nails it down."
Previous studies have shown that some people lack an enzyme called CYP2D6 that chemically alters codeine into morphine. The same enzyme metabolizes many drugs used to treat high blood pressure, heart arrhythmias, and depression. About 8 percent of whites, 6 percent of blacks, and 1 percent of Asians do not produce CYP2D6.
Currently, doctors tend to think that patients who don't respond to a pain-killing drug need higher doses. "Here's an example where a portion of the population will get no effect, and increasing their dose a lot more will still produce no effect," Wood says. "It's not that they're wimps or their pain is worse than [that of] other people."
All of the people in the current study, 10 white men from the United States and 8 men from China, possessed CYP2D6. Pain control is difficult to measure, so the researchers monitored how codeine affected breathing, blood pressure, and pupil dilation. Consistently, codeine affected the Chinese men less than the U.S. men. Their bodies cleared morphine faster and increased metabolism of codeine through enzymes other than CYP2D6.
No one knows whether the results shed any light on understanding addiction to opiates, Wood says. At first, he hypothesized that people who abuse codeine would possess CYP2D6, but his group realized that it would be difficult to find appropriate subjects.
Scientists once thought that ethnic differences in rates of alcoholism might have a biochemical basis. About half of Chinese and Japanese people flush uncomfortably after consuming alcohol because they lack the enzyme aldehyde dehydrogenase. Now, most scientists believe that social factors account for the alcoholism difference.
Not many researchers consider ethnicity when testing drugs, Wood says. Based on clinical studies of a "small, homogeneous population, we extrapolate dosage and toxicity with breathtaking confidence to worldwide use." In the case of codeine, the differences in metabolism aren't large enough to make toxicity a concern, says Nelson.
Knowledge of the important enzymes involved in metabolism, however, does spur drug companies to screen potential compounds very early, he says. "If the company is going to invest money in developing a drug, it wants to know if it won't work in a large percentage of the population."
Wood, A.J.J. 1997. Pharmacogenetic and ethnic differences in opiate response. Meeting of the American Chemical Society. Las Vegas.
Wendel L. Nelson
Department of Medicinal Chemistry
University of Washington
Seattle, WA 98195
Alastair J.J. Wood
Department of Pharmacology
Vanderbilt University School of Medicine
Room 552A, MRB
Nashville, TN 37232-6602
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