Session Examines Drug Interactions in Personalized Medicine

Evan Kharasch, M.D., Ph.D., said methadone is "very susceptible to drug interactions."

Evan Kharasch, M.D., Ph.D., said methadone is “very susceptible to drug interactions.”

Jag Khalsa, Ph.D., M.S., likens the possibility of genetic testing playing a role in treatment of patients to the arrival of Star Trek.

“I think in very near future we may be at a point when genetic testing is so cheap that we will be in a position to test if we find variability or nonresponse in a patient. We’ll say, ‘This guy does not have this enzyme, so let’s change the medication and treat him accordingly.’ Star Trek therapy is coming,” says Dr. Khalsa, Chief of the Medical Consequences Branch, Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on Drug Abuse.

Dr. Khalsa and Judith Martin, M.D, FASAM, Medical Director of the BAART Turk Street Clinic, San Francisco, led a Friday session, “Drug-Drug Interactions: Role of Individualized Medicine,” sponsored by the National Institute on Drug Abuse.

The program focused on the pharmacogenetic and pharmacodynamic interactions among recreational drugs and medications used in the treatment of patients with HIV. Research is emerging on pharmacogenomics to show that the genomic profile of CYP450s in patients could be used to design therapy for individual patients.

Evan Kharasch, M.D., Ph.D., looked at the pharmacogenetics of methadone, which, he says is “very susceptible to drug interactions” and influences plasma concentrations and clearance of methadone.

The state of the art has been that studies in vitro attribute the enzyme P4503A4 as being responsible for methadone metabolism, causing conventional wisdom to credit the enzyme for methadone metabolism and clearance clinically.

A lot of papers said methadone was going to be susceptible to CYP3A4-mediated drug interactions, says Dr. Kharasch, the Russell D. and Mary B. Shelden Professor of Anesthesiology, Director, Division of Clinical & Translational Research, Department of Anesthesiology, and a Professor of Biochemistry and Molecular Biophysics, and Vice Chancellor for Research, Washington University, St. Louis.

Dr. Kharasch and his fellow researchers found that CYP3A4 has little or no influence on plasma concentrations or CL of single-dose IV or oral methadone and in single-dose IV or oral methadone N-demethylation. He found that CYP2B6 is responsible for clinical methadone metabolism.

In his talk on “Integrating Substance Abuse Treatment Into HIV Care Settings,” Patrick G. O’Connor, M.D., M.P.H., Professor of Medicine and Chief of General Internal Medicine, Yale University School of Medicine, New Haven, Conn., described buprenorphine/naloxone (bup/nx) use in patients with HIV.

Dr. O’Connor says research indicates that bup/nx decreases drug-related but not sex-related HIV risk; drug outcomes improve in HIV-infected patients receiving bup/nx; bup/nx is safe in HIV-infected patients; on-site bup/nx leads to improved outcomes compared to off-site methadone; and naltrexone treatment in HIV-infected patients appears to be safe, and it’s effectiveness is being studied.

Zeruesenay Desta, Ph.D., Associate Professor of Medicine, Pharmacology and Toxiology, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, described the clinical use of efavirenz in HIV in his talk.

“I’m also a true believer in a personalized care. Patients do not respond or fail therapy because of a single thing,” Dr. Desta says.