Methadone effects on zidovudine disposition (AIDS Clinical Trials Group 262).
Large numbers of injection drug users (IDUs) are infected with HIV and receive both methadone and zidovudine (ZDV) therapy. Pharmacokinetic interactions between these agents may effect drug efficacy, toxicity, and compliance. To confirm and expand previous studies that identified a potential interaction between ZDV and methadone, we performed a within-subject study to determine oral and intravenous ZDV pharmacokinetics in 8 recently detoxified, heroin-addicted patients with HIV disease before and after initiation of methadone treatment. Acute methadone treatment increased oral ZDV in the area under the curve (AUC) by 41% (p = .03) and intravenous ZDV AUC by 19% (p = .06). Clearance was reduced by 21% (p = .007) and 19% (p = .04), respectively. Chronic methadone treatment increased oral ZDV AUC by 29% (p = .15) and intravenous ZDV AUC by 41% (p = .05). Clearance was decreased by 26% for both routes (p = .02). Methadone levels remained in the therapeutic range during ZDV treatment. These effects resulted primarily from inhibition of ZDV glucuronidation, but also from decreased renal clearance of ZDV. This study confirms that methadone-maintained patients receiving standard ZDV doses experience greater ZDV exposure and may be at increased risk for ZDV side effects and toxicity. Increased toxicity surveillance and possibly reduction in ZDV dose are indicated when these two agents are given concomitantly.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
E F
EF
McCance-Katz
P M
PM
Rainey
P
P
Jatlow
G
G
Friedland
D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006556:Heroin Dependence / Q000150:complications / Q000378:metabolism / Q000534:rehabilitation*; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008691:Methadone / Q000494:pharmacology* / Q000627:therapeutic use; D009294:Narcotics / Q000494:pharmacology* / Q000627:therapeutic use; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D009294:Narcotics; D015215:Zidovudine; D008691:Methadone