London scientists lead the way in drug interaction research

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A team of London scientists is changing the way health-care professionals look at natural products like “health foods” and herbal remedies. It has become increasingly accepted that these products have the potential to alter the action of certain drugs. The outcome can be adverse clinical effects ranging from toxicity to loss of benefit of medications. Dr. David Bailey, scientist at the Lawson Health Research Institute, Department of Medicine at London Health Sciences Centre, and Department of Physiology and Pharmacology, The University of Western Ontario, has been working towards improving our understanding of the causes of these adverse drug interactions and their management.

Dr. Bailey and fellow Lawson scientist Dr. George Dresser, Department of Medicine, The University of Western Ontario were recently approached by the Canadian Medical Association Journal (CMAJ 2004; 170:1531-32) to comment on their findings regarding natural products and effects on drugs. According to Drs. Bailey and Dresser, the public generally considers natural products to be safe and beneficial. Often the patient does not see the need to tell their doctor that they are using these products and the doctor does not routinely ask. In the article, Drs. Bailey and Dresser look at two commonly used products – grapefruit juice and St. John’s wort – to address the mechanisms, clinical problems and clinical approaches of adverse drug interactions.

Recent studies have shown that natural products can interact with drugs through affecting the biological processes that regulate drug metabolism and elimination. Previously, Dr. Bailey and fellow Lawson scientists Dr. J. David Spence and Dr. Malcolm Arnold made the initial finding that grapefruit can markedly reduce the activity of the intestinal drug metabolizing enzyme CYP3A4, thereby markedly elevating the percentage of the drug that reaches the systemic circulation, possibly attaining toxic levels. “Sixty per cent of drugs that are commonly prescribed are metabolized to some extent by CYP3A4,” remarks Dr. Bailey. The result of the inhibition of this enzyme can be significant. For example, according to Dr. Bailey, taking certain medications with a glass of grapefruit juice is the same as taking 12-15 tablets of the same medication with a glass of water.

St. John’s wort has the opposite effect. It increases the activity of CYP3A4 thereby decreasing the percentage of the drug in the system, potentially leading to diminished clinical response. In addition, St. John’s wort increases the activity of the drug efflux transporter P-glycoprotein, which acts to pump drugs back into the intestine. The combination of enhanced activity of intestinal CYP3A4 and P-glycoprotein induced by St. John’s wort can substantially reduce the efficacy of drugs. Studies have shown that this effect can last for up to a week after discontinuing use of St. John’s wort. “The clinical consequences of lessened drug efficacy can be as devastating as those of enhanced drug toxicity,” remarks Dr. Dresser, “St. John’s wort has been linked to organ rejection and increased HIV viral load.”

Drs. Bailey and Dresser say physicians should be wary of abrupt and unexplained changes in the clinical status of a patient. They recommend that physicians take careful dietary and herbal histories as an initial approach. Rather than immediately altering medications, eliminating certain natural products from the diet may be a more effective strategy. Moreover, most herbal products have not been assessed for their potential to cause drug interactions. “As a general rule, we recommend discouraging the use of such products for which there is no information,” says Dr. Bailey.

Drs. Bailey and Dresser have also developed a physician-peer education program to help doctors understand the multifactorial nature of drug interactions. This program has been widely accepted by the health care profession as doctors from coast to coast recognize the pressing need to learn more about drug interactions.

Most recently, Drs. Bailey and Dresser received a grant for $267,396 from the Canadian Institutes of Health Research to study the involvement of diet and intestinal drug uptake transporters. They hope this novel research will extend the understanding and clinical management of successful drug use.

The Lawson Health Research Institute in London, Ontario, Canada is the research arm of London Health Sciences Centre, and St. Joseph’s Health Care London.