Steady-state pharmacokinetics of bupropion SR in juvenile patients.
OBJECTIVE
To examine the steady-state pharmacokinetic properties of bupropion sustained release (SR) and their potential developmental differences in youths.


METHODS
Eleven boys and eight girls aged 11 to 17 years old were prescribed bupropion SR monotherapy for attention-deficit/hyperactivity disorder (n = 16) and/or depressive disorders (n = 16). Bupropion SR was given in morning doses of 100 mg/day (n = 11) or 200 mg/day (n = 8) for 14 days or less, with five subjects studied on both doses. All subjects had blood draws from an intravenous port every 1 to 3 hours for 24 hours after their usual morning doses. Pharmacokinetic variables were determined by noncompartmental and compartmental analyses for bupropion and metabolites, respectively.


RESULTS
Bupropion and its metabolites exhibited linear pharmacokinetics. Areas under the concentration curves for the hydroxybupropion, threohydrobupropion, and erythrohydrobupropion were 20, 12, and 2.7 times higher, respectively, than for bupropion. Relative to adults, the mean half-lives of bupropion (12.1 hours) and threohydrobupropion (26.3 hours) were significantly shorter, and areas under the concentration curve ratios of metabolites to bupropion were 19% to 80% higher.


CONCLUSIONS
Youths metabolize bupropion SR faster to hydroxybupropion and other active metabolites than adults. Until the clinical importance of bupropion's metabolites is clarified, bupropion SR should be given in divided doses to youths, as the manufacturer recommends for adults taking higher doses.
Daviss
W Burleson
WB
Western Psychiatric Institute and Clinic, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. davisswb@upmc.edu
Perel
James M
JM
Rudolph
George R
GR
Axelson
David A
DA
Gilchrist
Richard
R
Nuss
Sharon
S
Birmaher
Boris
B
Brent
David A
DA
D000293:Adolescent; D000367:Age Factors; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D016642:Bupropion / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002648:Child; D003692:Delayed-Action Preparations; D003866:Depressive Disorder / Q000188:drug therapy; D005260:Female; D006207:Half-Life; D006803:Human Development; D006801:Humans; D016014:Linear Models; D008297:Male
D018687:Antidepressive Agents, Second-Generation; D003692:Delayed-Action Preparations; D016642:Bupropion