LACK OF A PHARMACOLOGICAL INTERACTION BETWEEN RIFABUTIN AND METHADONEIN HIV-INFECTED FORMER INJECTING DRUG-USERS

Rifampin, an agent known to decrease the half-life of methadone, and r ifabutin are two rifamycins that are structurally similar and share me chanisms of action. Hence the possibility of a drug-drug interaction b etween rifabutin and methadone was evaluated in 24 methadone-maintaine d, former injecting drug users infected with the human immunodeficienc y virus. The study was an open-label, drug-drug interaction and safety trial in which patients were followed for 15 days. Each patient recei ved rifabutin 300 mg as a single dose concomitantly with their daily i ndividualized methadone dosage. No significant differences in methadon e peak plasma concentration, time to peak plasma concentration, area u nder the plasma concentration-time curve, systemic clearance or renal clearance was observed in the presence of rifabutin. Seventy-five perc ent of the patients reported at least one symptom of narcotic withdraw al 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 rifab utin 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 pharmac okinetics of methadone in these patients.