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 wit hin-subject study to determine oral and intravenous ZDV pharmacokineti cs in 8 recently detoxified, heroin-addicted patients with HIV disease before and after initiation of methadone treatment. Acute methadone t reatment 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 tr eatment 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 tre atment. These effects resulted primarily from inhibition of ZDV glucur onidation, but also from decreased renal clearance of ZDV. This study confirms that methadone-maintained patients receiving standard ZDV dos es experience greater ZDV exposure and may be at increased risk for ZD V side effects and toxicity. Increased toxicity surveillance and possi bly reduction in ZDV dose are indicated when these two agents are give n concomitantly.