title: Single-dose pharmacokinetics of bupropion hydrobromide and metabolites in healthy adolescent and adult subjects.
abstract: Data from 2 pediatric single-dose studies, conducted at the same center, were combined to evaluate exposure levels of bupropion and metabolites in adolescents 12-17 years old, compared with adults > 18 years. Pharmacokinetic analyses of bupropion and its metabolites were performed using normalization and pharmacological/convulsive weighting methods on exposure. When compared with adults (>18 years), subjects 12-14 years had an increase in weight-normalized exposure to bupropion (ie, Cmax , 78%; AUC0-t , 83%; and AUCinf , 85%). Variability in this younger age group was also higher, with observations of a 3- to 4-fold increase in exposure. When the changes in metabolites were accounted within pharmacological and convulsive-weighted exposures, the relative ratio of 12-14 years to adults in body weight-normalized Cmax was 127% and 110%, respectively. Subjects 15-17 years did not exhibit a difference in exposure compared with adults. The influence of age on bupropion pharmacokinetics demonstrates that, in general, healthy adolescent subjects cannot be considered smaller healthy adult subjects; the increase in exposure is inversely related to age and appears to be solely associated with bupropion, not with its metabolites. Because there are no clinical safety and efficacy data of bupropion in adolescents, this data may shift its risk-benefit profile.
authors.affiliation: Valeant Pharmaceuticals North America, LLC, Bridgewater, NJ, USA.
authors.forename: D Alexander
authors.initials: DA
authors.lastname: Oh
authors.affiliation: Valeant Pharmaceuticals North America, LLC, Bridgewater, NJ, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Crean
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D001965:Bromides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D016642:Bupropion / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D005431:Florida; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D001965:Bromides; D016642:Bupropion
keywords: CYP2B6; adolescents; bupropion; exposure; metabolite; pediatrics; variability