Indinavir versus Methadone
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Study Design
This was a multiple-dose, blinded, randomized, two- period, crossover study. Twelve patients, who were on methadone maintenance (20 mg to 60 mg q.a.m.), received, in randomized order, 2 different treatments, each for 8 days: indinavir (IDV) 800 mg qSh with methadone q.a.m and IDV placebo with methadone q.a.m. Phar- macokinetic sampling was performed for methadone and its pyrroli- dine metabolite with and without IDV and for IDV with methadone.
Study Results
For methadone (n=12) in combination with IDV vs methadone alone, geometric mean ratio (90% C.I.) for the AUC(0-:4 hr) was 0.96 (0.86, 1.06) indicative of no significant effect on methadone pharmacokinetic parameters were also similar. There was also no significant effect on the plasma concentrations of the methadone pyrrolidine metabolite, EDDP. For lDV (n=12) in combi- nation with methadone vs IDV alone historical data (four studies in healthy subjects), the geometric mean ratios ranged from 0.81 to 1.10 for AUC(0_ s br), indicative of no significant effect of methadone on the overall exposure to IDV. The plasma profile of IDV when coad- ministered with methadone appeared to be altered, with 16 to 36% lower Cma x values and 50 to 100% higher C s hr (trough) values. These findings may be attributed to opioid effects on gastrointestinal motil- ity. The increase in Cg ~ and small decrease in Cra ~ with no change in AUC(0. s hf), would not be anticipated to adversely effect the effi- cacy or safety of IDV.
Study Conclusions
IDV can be administered with methadone without dose modification of either drug.
References
Cantilena L, McCrea J, Blazes D, Winchell G, Carides A, Royce C, Deutsch P. Lack of a pharmacokinetic interaction between indinavir and methadone. Clinical Pharmacology & Therapeutics. 1999; 2: 135-145.
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