This is an archived article.

May 27, 1997

Enzymes targeted as key to understanding of drug interactions

You go to one doctor for your back problem. You see another for high blood pressure. Perhaps you consult a third for a nagging sinus infection. As part of your treatment, each writes a prescription or two. The result can be an array of pill bottles on your bathroom counter or breakfast table, perhaps augmenting your usual arsenal of over-the-counter supplements and pain and cold remedies.
How is the patient — or the health care professional — to know when the potential exists for a serious, even life-threatening, interaction between medications? Or when one drug may render another ineffective? News stories have highlighted the problem of pharmacists who failed to question prescriptions for dangerous drug combinations, and pharmacists complain of computer programs that fail to give them adequate warning of possible interactions.

A notorious example of a potentially deadly drug duo was Seldane, a popular antihistamine, and erithromycin, a common antibiotic, which when taken together could produce sometimes fatal heart problems. The U.S. Food and Drug Administration (FDA) has recommended that Seldane be withdrawn from the market.

Prevention of drug interactions, say researchers at the University of Washington School of Pharmacy, lies in learning how the human body processes each drug.

The school has recently established a formal Program in Drug Interactions, tapping the expertise of 22 faculty members believed to be the largest group of experts in the world on drug interactions.

The UW investigators are seeking systematic knowledge of how various enzymes — biochemical catalysts produced by the body — metabolize drugs. Their research is producing an understanding of the potential for adverse effects among thousands of drug combinations.

“Pharmacists have had to remember hundreds of pairs of drugs that interact,” said the program’s director, Dr. Rene Levy, professor and chair of pharmaceutics. “But there was a shift in our knowedge in the late 1980s. Instead of dealing with pairs of drugs, we began to focus on the four or five enzymes that metabolize most drugs. If the patient is taking two drugs that are metabolized by the same enzyme, there can be an interaction.”

Funded by grants from the National Institutes of Health, Dr. William Trager, professor of medicinal chemistry, has led a team of School of Pharmacy researchers investigating such drug interactions for more than a decade.

“There are simple test-tube methods to determine which enzyme metabolizes a new drug,” said Levy. “While we are still in the research phase, we are already performing these analyses for the pharmaceutical industry. In fact, as new drugs are developed, the FDA now requires as part of its approval process that the enzymes that metabolize them be identified.

“In the future, doctors and pharmacists will be able to select a drug treatment based on criteria that include the potential for interaction,” said Levy. “We have begun developing computerized databases for use by pharmaceutical companies, pharmacists and physicians.”

The UW Program in Drug Interactions has taken its efforts beyond research to outreach, by means of conferences, continuing education courses for pharmacists and articles in professional journals and newsletters. Pharmacy professors Dr. Philip Hansten and Dr. John Horn have recently authored an expanded version of their book, Drug Interactions: Analysis and Management, to help health care professionals manage potential drug interactions in their patients.

“There has been much publicity on the bad news about drug interactions,” Levy said, “but this is the good news: There has been rapid progress in understanding them, and we now have a new method of detecting serious interactions.”

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