Abstract
Wellbutrin (bupropion•HCl), a novel antidepressant in current clinical use, was evaluated in two pharmacokinetic, steady-state studies. Bupropion (B), and its 3 basic metabolites, hydroxy-t-butyl-bupropion (HB), erythro-hydro-bupropion (EB), and threo-hydro-bupropion (TB) plasma concentrations were determined by a high pressure liquid chromatographic method at several time points on the fourteenth day of each dosing regimen. Based on mean AUC and Cmax ratios from 22 male subjects, dose proportionality was observed between 100 and 150 mg t.i.d. Mean AUC0→6 ratios were 1.38 for B, 1.46 for HB, 1.54 for EB, and 1.42 for TB at 150 mg compared to 100 mg. Corresponding ratios for Cmax were 1.35, 1.49, 1.69, and 1.49, respectively, for the 4 compounds while Cmin ratios were 1.41, 1.45, 1.39, and 1.38, respectively. Fluctuation index ratios averaged 0.99, 1.21, 1.46, and 1.27 for the 4 compounds, respectively. Mean Tmax values at 100 vs. 150 mg were 1.5 and 1.5 hr for B, 2.8 and 3.4 hr for HB, 2.9 and 3.8 hr for EB, and 3.1 and 3.5 hr for TB. Half-lives were found to be 21 hr for B, 20 hr for HB, 33 hr for EB, and 37 hr for TB. In a second steady-state study in 14 subjects, bioequivalence parameters were compared at 150 mg b.i.d. vs. 100 mg t.i.d. Mean AUC0→24 ratios for the two dosing regimens were 0.98 for B, 0.95 for HB, 0.98 for EB, and 1.00 for TB, and Cmax ratios were 1.20, 1.07, 1.02, and 1.04, respectively. Corresponding ratios for Cmin were 0.98, 0.92, 0.94, and 0.97, respectively, for these 4 entities, while fluctuation index ratios averaged 1.26, 1.42, 1.24, and 1.26, respectively. Thus, 150 mg b.i.d and 100 mg t.i.d. yield equivalent AUC values, however, the mean Cmax for bupropion was 20% greater with b.i.d. dosing.
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Schroeder, D., Fleck, R., Hinton, M. et al. Wellbutrin in Volunteer Studies -- Kinetics and Dose Proportionality of Bupropion and its Metabolites. Neuropsychopharmacol 11, 283 (1994). https://doi.org/10.1038/sj.npp.1380204
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DOI: https://doi.org/10.1038/sj.npp.1380204