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New information points to safer methadone use for treatment of pain and addiction
Date:3/3/2009

clearing methadone from the body. So the package insert appears to be incorrect, or certainly needs to be reevaluated, as do guidelines that explain methadone dosing and potential drug interactions."

That can be dangerous, Kharasch explains, because a clinician may prescribe too much or too little methadone for patients taking drugs that interact with P4503A, having been informed that they also would influence methadone clearance. Too little methadone will not relieve pain. Too much can contribute to the unintentional build-up of methadone in the system, which can cause slow or shallow breathing and dangerous changes in heartbeat. Physicians could be unintentionally prescribing methadone incorrectly.

"The highest risk period for inadequate pain therapy or adverse side effects is during the first two weeks a patient takes methadone," Kharasch says. "If we can provide clinicians with better dosing guidelines, then I believe we will be able to better treat pain and limit deaths and other adverse events."

About a dozen related liver enzymes are part of the P450 family, and Kharasch believes another enzyme from that family may be the one actually involved in methadone metabolism and clearance. His laboratory is determined to identify the correct enzyme to limit over-and under-dosing of patients taking methadone to improve addiction and pain treatment as well as patient safety. Currently, he's testing the related enzyme P4502B. Laboratory studies and preliminary clinical results indicate that P4502B may be involved, but he says more clinical research is needed.

"The research also is important for the treatment of HIV-AIDS," Kharasch says. "Protease inhibitors can interfere with the activity of P4503A but increase the activity of P4502B. This paradox is highly unusual, and because these two enzymes metabolize so many prescription drugs, there are many potential drug interactions that we'll be able to understand better if we can get a be
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Contact: Jim Dryden
jdryden@wustl.edu
314-286-0110
Washington University School of Medicine
Source:Eurekalert  

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