Enzymes,Ethnicity Create Dramatic Differences In Codeine's Effectiveness In Humans

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ENZYMES,ETHNICITY CREATE DRAMATIC DIFFERENCES IN CODEINE'S EFFECTIVENESS IN HUMANS

LAS VEGAS, Sept. 8 -- The pain-relieving drug codeine is totally ineffective in some ethnic groups -- including one in ten whites -- according to new findings presented here today at a national meeting of the American Chemical Society. The report shows a variety of differences in the drug's effectiveness and side effects, based on a person's ethnicity.

Researchers and physicians have long known that responses to any drug vary from person to person, and that some populations (the elderly, for example) can be more sensitive than others. New research presented at the meeting by Dr. Alastair Wood, a clinical pharmacologist at Vanderbilt University in Nashville, however, shows that codeine is unusual because the lion's share of its effect comes not from the drug itself, but from a substance the body makes from it. That substance, or metabolite, is morphine, and the enzyme that manufactures it is called CYP2D6. Wood's research indicates that about 10 percent of Caucasians lack this enzyme, and thus are unable to convert codeine to morphine to relieve their pain.

"Most drugs themselves produce the effect -- so if a patient doesn't get the effect, the physician gives more of the drug," says Wood, a clinical pharmacologist at Vanderbilt University. "But here's a situation in which a proportion gets no effect -- it's actually predictable."

Wood's research also indicates that about 2 percent of Chinese lack CYP2D6; but even those who do have the enzyme produce less morphine. Furthermore, that morphine has less effect, even when the concentration in their bloodstreams is the same as in Caucasians. On the other hand, Chinese subjects were significantly more likely to suffer the nauseating side effects of codeine than Caucasians. Wood examined characteristics of respiration to monitor effects in his subjects, such as suppression of breathing rate and stimulation of aspiration.

The enzyme CYP2D6 metabolizes a wide variety of drugs in addition to codeine: propranolol (Inderal), which treats high blood pressure; propafenone (Rythmol), for heart arrythmias; haloperidol (Haldol), for certain mental illnesses; and many of the tricyclic antidepressants. Since these drugs influence the body themselves, people who are missing CYP2D6 usually experience exaggerated effects when taking these medications -- not the lack of effect that metabolite-dependent codeine causes.

Paper TOXI 7 will be presented at 3:15 p.m., Mon., Sept. 8, in the Convention Center, Room N120, Level One.

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The national meeting of the American Chemical Society, the world's largest scientific society, will be held in Las Vegas Sept. 7 - 11. This paper is among 4,500 presentations that will be made.