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Bupropion in Depression:  II. The Role of Metabolites in Clinical Outcome

Robert N. Golden, MD; C. Lindsay DeVane, PharmD; S. Casey Laizure, PharmD; Matthew V. Rudorfer, MD; Michael A. Sherer, MD; William Z. Potter, MD, PhD
Arch Gen Psychiatry. 1988;45(2):145-149. doi:10.1001/archpsyc.1988.01800260055007.
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• We studied the steady-state pharmacokinetics of bupropion hydrochloride, a unicyclic aminoketone antidepressant, in depressed patients. The metabolites hydroxybupropion (HB), threohydrobupropion, and erythrohydrobupropion predominated over the parent compound in plasma and cerebrospinal fluid at steady state. Plasma concentrations of each metabolite correlated with cerebrospinal fluid concentrations. Higher plasma metabolite concentrations were associated with poor clinical outcome. This relationship was most striking with HB; plasma HB levels were greater than 1250 ng/mL in all five nonresponders and less than 1200 ng/mL in all seven responders. Plasma HB levels correlated with postreatment plasma homovanillic acid levels. High levels of bupropion metabolites may be associated with poor clinical outcome due to toxic effects involving dopaminergic systems. Alternatively, a curvilinear dose-response relationship may exist for bupropion metabolites. Future studies should explore the clinical utility of plasma metabolite measurements in enhancing the efficacy of treatment with bupropion.

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