title: Effect of renal impairment on the pharmacokinetics of bupropion and its metabolites.
abstract: OBJECTIVE
  To investigate the effect of kidney disease on bupropion pharmacokinetics and on cytochrome P450 (CYP) 2B6 activity as measured by bupropion hydroxylation.
  
  
  METHODS
  In an open parallel group study, 17 healthy, nonsmoking subjects and 10 patients with impaired kidney function received a single 150 mg oral dose of sustained release bupropion. Plasma concentrations of bupropion and its metabolites were measured for up to 72 h. Subjects were genotyped for the CYP2B6 SNPs 1459 C>T, 785 A>G and 516 G>T.
  
  
  RESULTS
  Bupropion AUC was 126% higher (P < 0.0001, 95% CI +72%, +180%), C(max) 86% higher (P = 0.001, 95% CI +40%, +131%), CL/F 63% lower (P = 0.001, 95% CI -29%, -96%), and t(1/2) 140% longer (P = 0.001, 95% CI +76%, +204%) in renally impaired patients. However, only minor changes were detected in the concentrations of the metabolites. In renally impaired subjects the hydroxybupropion : bupropion AUC ratio was decreased by 66% (P = < 0.0001, 95% CI -19%, -114%) and the hydrobupropion : bupropion AUC ratio by 69% (P = 0.001, 95% CI +8%, -146%) compared with controls.
  
  
  CONCLUSIONS
  The CL/F of bupropion was significantly lower in subjects with renal impairment. Because the principal metabolites of bupropion possess similar pharmacological activity to the parent compound, dosage recommendations for patients with renal impairment cannot be given. A direct effect of renal impairment on CYP2B6 activity could not be demonstrated by the present study design.
authors.affiliation: Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland. miia.turpeinen@oulu.fi
authors.forename: Miia
authors.initials: M
authors.lastname: Turpeinen
authors.forename: Niina
authors.initials: N
authors.lastname: Koivuviita
authors.forename: Ari
authors.initials: A
authors.lastname: Tolonen
authors.forename: Petri
authors.initials: P
authors.lastname: Reponen
authors.forename: Stefan
authors.initials: S
authors.lastname: Lundgren
authors.forename: Jouko
authors.initials: J
authors.lastname: Miettunen
authors.forename: Kaj
authors.initials: K
authors.lastname: Metsärinne
authors.forename: Anders
authors.initials: A
authors.lastname: Rane
authors.forename: Olavi
authors.initials: O
authors.lastname: Pelkonen
authors.forename: Kari
authors.initials: K
authors.lastname: Laine
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000493:pharmacokinetics*; D016642:Bupropion / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D005260:Female; D005838:Genotype; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D016642:Bupropion; D003577:Cytochrome P-450 Enzyme System