Lack of a pharmacologic interaction between rifabutin and methadone in HIV-infected former injecting drug users.
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 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.
Brown
L S
LS
Addiction Research and Treatment Corporation, Brooklyn, NY 11201, USA.
Sawyer
R C
RC
Li
R
R
Cobb
M N
MN
Colborn
D C
DC
Narang
P K
PK
D017088:AIDS-Related Opportunistic Infections / Q000097:blood* / Q000188:drug therapy; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D009293:Opioid-Related Disorders / Q000097:blood* / Q000534:rehabilitation; D017828:Rifabutin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015819:Substance Abuse, Intravenous / Q000097:blood* / Q000534:rehabilitation; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000534:rehabilitation; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000188:drug therapy
D017828:Rifabutin; D008691:Methadone