Drug-Drug Interactions of Methadone

Antiretroviral drugs Methadone is often used for opioid replacement therapy in intravenous drug abusers. The incidence of HIV infection is significantly higher in this population than in the general public, and interactions with drugs used for the treatment of AIDS are therefore important. Methadone is predominantly metabolized by CYP3A4. Antiretroviral therapy with a non-nucleoside reverse transcriptase inhibitor (for example efavirenz, abacavir, and nevirapine) and/or a protease inhibitor (for example amprenavir) will induce the metabolism of methadone. This therapeutic combination is becoming increasingly common in HIV-positive substance misusers. Two studies have explicitly shown a significant reduction of methadone concentration by 28-87%. In the first study, 11 patients taking methadone maintenance therapy were given efavirenz and had a mean increase in methadone dosage requirement of 22%. In the second study, five methadone-maintained opioid-dependent individuals were given a combination of abacavir and amprenavir; the methadone concentration fell to 35% of the original concentration within 14 days. In a prospective study of 54 patients taking antiretroviral drugs who also took methadone and a further Read more […]

Drug-Drug Interactions of Heroin

Alcohol Many heroin users use heroin and alcohol together. There has been an evaluation of the pharmacokinetic interaction between heroin and alcohol and the role of that interaction in the cause of 39 heroin-related deaths that were attributed to either heroin or heroin + ethanol. The cases were arbitrarily divided into two groups according to blood ethanol concentration (low-ethanol group, under 1000 ng/ml, and high ethanol group, over 1000 μg/ml. The high-ethanol group was associated with reduced hydrolysis of 6-acetylmorphine to morphine, and there was an inverse correlation between blood ethanol concentration and hydrolysis of 6-acetylmorphine to morphine. The concentration of total morphine was lower in the high-ethanol group. High blood ethanol concentrations were also associated with an increased ratio of unbound to total morphine and with reduced excretion of unbound and total morphine. The relative concentrations of conjugated heroin metabolites were reduced in the presence of a high blood ethanol concentration. The authors hypothesized that alcohol inhibits the glucuronidation of morphine, resulting in less conjugated morphine in the blood. Thus, in patients with high blood ethanol concentrations the additional Read more […]