Pharmacokinetic interactions of zidovudine and methadone in intravenous drug-using patients with HIV infection.
Pharmacokinetic parameters for methadone and zidovudine (ZDV), alone and in combination, were determined in 14 HIV-infected individuals including nine former intravenous drug users (IVDU) who were receiving methadone maintenance therapy. The serum levels of methadone were measured prior to and after initiation of ZDV treatment, with each patient serving as his or her own control. Concurrent administration of ZDV did not alter either the peak methadone concentration or the area under the methadone concentration-time curve (AUC). Serum and urine ZDV and ZDV-glucuronide concentrations were measured by both high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA), and pharmacokinetic parameters determined at least twice in each of nine methadone-maintained former IVDU patients initiating ZDV therapy. These parameters were compared to those for ZDV in a group of five control patients who were neither receiving methadone nor had a history of i.v. drug use. The serum ZDV levels were significantly higher in the methadone patients, with a 43% increase (p less than 0.05) over the mean AUC of 7.68 microM h observed in the control patients. Furthermore the methadone patients could be divided into two groups based on their ZDV AUC: four patients whose ZDV AUC averaged twofold higher than the control group, and five patients whose ZDV AUC were equal to control. No significant differences were found between the control and methadone groups for ZDV bioavailability or Tmax, serum half-life, glucuronidation, or urinary excretion. Methadone also did not affect ZDV glucuronidation in an in vitro assay using human hepatic microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)
Schwartz
E L
EL
Department of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York 10467.
Brechbühl
A B
AB
Kahl
P
P
Miller
M A
MA
Selwyn
P A
PA
Friedland
G H
GH
D000328:Adult; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008691:Methadone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D015819:Substance Abuse, Intravenous / Q000150:complications / Q000188:drug therapy*; D015215:Zidovudine / Q000493:pharmacokinetics* / Q000627:therapeutic use
D015215:Zidovudine; D008691:Methadone