Lack of a pharmacologic interaction between rifabutin and methadone in HIV-infected former injecting drug users

• Published in: Drug and alcohol dependence 1996-12, Vol.43 (1), p.71-77
• Main Authors: Brown, Lawrence S., Sawyer, Robert C., Li, Ronald, Cobb, Malik N., Colborn, David C., Narang, P.K.
• Format: Article
• Language: English
• Subjects: Adult; AIDS-Related Opportunistic Infections - blood; AIDS-Related Opportunistic Infections - drug therapy; Biological and medical sciences; Dose-Response Relationship, Drug; Drug addictions; Drug Interactions; Drug Therapy, Combination; Female; HIV Infections - blood; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Injecting drug users; Interactions; Male; Medical sciences; Metabolic Clearance Rate; Methadone; Methadone - administration & dosage; Methadone - adverse effects; Methadone - pharmacokinetics; Middle Aged; Narcotic withdrawal; Neurologic Examination - drug effects; Opioid-Related Disorders - blood; Opioid-Related Disorders - rehabilitation; Pharmacokinetics; Rifabutin - administration & dosage; Rifabutin - adverse effects; Rifabutin - pharmacokinetics; Substance Abuse, Intravenous - blood; Substance Abuse, Intravenous - rehabilitation; Substance Withdrawal Syndrome - blood; Substance Withdrawal Syndrome - rehabilitation; Toxicology; Tuberculosis, Pulmonary - blood; Tuberculosis, Pulmonary - drug therapy
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/S0376-8716(97)84352-9

Rifampin, an agent known to decrease the half-life of methadone, and rifabutin are two rifamycins that are structurally similar and share mechanisms of action. Hence the possibility of a drug-drug interaction between rifabutin and methadone was evaluated in 24 methadone-maintained, former injecting drug users infected with the human immunodeficiency virus. The study was an open-label, drug-drug interaction and safety trial in which patients were: followed for 15 days. Each patient received rifabutin 300 mg as a single dose concomitantly with their daily individualized methadone dosage. No significant differences in methadone peak plasma concentration, time to peak plasma concentration, area under the plasma concentration-time curve, systemic clearance or renal clearance was observed in the presence of rifabutin. Seventy-five percent of the patients reported at least one symptom of narcotic withdrawal during the study, however, these symptoms were mild. A relationship between the development of narcotic withdrawal and methadone systemic exposure could not be established. Concurrent administration of rifabutin and methadone appeared to be safe in human immunodeficiency virus-infected injecting drug users maintained on stable doses of methadone and is not expected to produce any significant changes in the pharmacokinetics of methadone in these patients.