title: Dose-related reduction in bupropion plasma concentrations by ritonavir.
abstract: The effect of repeat oral doses of ritonavir, at high (600 mg twice daily) and low (100 mg twice daily) doses, on the pharmacokinetics of a single dose of bupropion was evaluated in healthy volunteers. Subjects received a single dose of 150 mg of bupropion on day 1 and twice-daily ritonavir from day 8 through day 30. Ritonavir was up-titrated from 300 mg twice daily to 600 mg twice daily in the high-dose ritonavir study, whereas subjects remained on 100 mg twice-daily ritonavir in low-dose ritonavir study. Subjects received a second single dose of bupropion on day 24. Serial blood samples were obtained to evaluate the pharmacokinetics of bupropion and its metabolites on days 1 and 24. Steady-state ritonavir led to a decrease of area under the curve and maximum plasma concentration of bupropion by 62% to 67% in the high-dose study and by 21% to 22% in the low-dose study, indicating a drug interaction of statistical and clinical significance, particularly at high doses of ritonavir. These studies demonstrate that the reduction of bupropion exposure by ritonavir is dose-related. Dosage adjustment of bupropion may be needed when administered with ritonavir. However, the maximum recommended daily dose of bupropion should not be exceeded.
authors.affiliation: GlaxoSmithKline, PharmD, 5 Moore Drive, GlaxoSmithKline, Research Triangle Park, NC, USA. joohyun.x.park@gsk.com
authors.forename: Joohyun
authors.initials: J
authors.lastname: Park
authors.forename: Marika
authors.initials: M
authors.lastname: Vousden
authors.forename: Claire
authors.initials: C
authors.lastname: Brittain
authors.forename: Donavon J
authors.initials: DJ
authors.lastname: McConn
authors.forename: Laura
authors.initials: L
authors.lastname: Iavarone
authors.forename: John
authors.initials: J
authors.lastname: Ascher
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Sutherland
authors.forename: Keith T
authors.initials: KT
authors.lastname: Muir
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016642:Bupropion / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003692:Delayed-Action Preparations; D017320:HIV Protease Inhibitors; D016642:Bupropion; D019438:Ritonavir