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A study of a dopaminergic antidepressant that may have an advantageous profile for use in elderly patients, bupropion, was conducted to determine the pharmacokinetics of bupropion in the elderly. Pharmacokinetics of single- and multiple-dose bupropion were examined in six elderly patients (five women and one man) diagnosed with depression. Mean (±SD) CLapp of bupropion was 1.6 ± 0.4 L/hr/kg, approximately 80% of the corresponding value reported for younger patients. Mean bupropion t1/2 was 34.2 ± 8.7 hours, and average apparent Vd (Vdapp) was 79.3 ± 29.4 L/kg. Apparent half-lives (t1/2 app) of the metabolites hydroxybupropion, erythrobupropion, and threohydrobupropion were 34.2 ± 4.6 hours, 61.4 ± 21.6 hours, and 38.8 ± 7.6 hours, respectively. After multiple dosing, the mean t1/2 for bupropion and its metabolites did not change significantly, although in some patients the t1/2app of the metabolites was substantially prolonged. There was also evidence of inordinate accumulation of metabolites. The elderly are at risk for accumulation of bupropion and its metabolites. Specification of therapeutic drug monitoring parameters for bupropion treatment of the elderly is needed.