AIMS: 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.
AIMS: 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: M Hidestrand; M Oscarson; J S Salonen; L Nyman; O Pelkonen; M Turpeinen; M Ingelman-Sundberg Journal: Drug Metab Dispos Date: 2001-11 Impact factor: 3.922
Authors: Albert W Dreisbach; Shanker Japa; Aster B Gebrekal; Sarah E Mowry; Juan J L Lertora; Burde L Kamath; Allan E Rettie Journal: Clin Pharmacol Ther Date: 2003-05 Impact factor: 6.875
Authors: S R Faucette; R L Hawke; E L Lecluyse; S S Shord; B Yan; R M Laethem; C M Lindley Journal: Drug Metab Dispos Date: 2000-10 Impact factor: 3.922
Authors: C L DeVane; S C Laizure; J T Stewart; B E Kolts; E G Ryerson; R L Miller; A A Lai Journal: J Clin Psychopharmacol Date: 1990-10 Impact factor: 3.153
Authors: Julia Kirchheiner; Christian Klein; Ingolf Meineke; Johanna Sasse; Ulrich M Zanger; Thomas E Mürdter; Ivar Roots; Jürgen Brockmöller Journal: Pharmacogenetics Date: 2003-10
Authors: Thomas C Dowling; Andrew E Briglia; Jeffrey C Fink; Donna S Hanes; Paul D Light; Lucy Stackiewicz; Chetan S Karyekar; Natalie D Eddington; Matthew R Weir; William L Henrich Journal: Clin Pharmacol Ther Date: 2003-05 Impact factor: 6.875
Authors: Bruce K Birmingham; Suzanne K Swan; Tom Puchalski; Pat Mitchell; Connie Azumaya; Julie Zalikowski; Yi Wang Journal: Clin Drug Investig Date: 2013-04 Impact factor: 2.859
Authors: Melanie S Joy; Reginald F Frye; Kristi Stubbert; Kim R Brouwer; Ronald J Falk; Evan D Kharasch Journal: J Clin Pharmacol Date: 2010-01-26 Impact factor: 3.126
Authors: Andrew S Kucey; Thomas J Velenosi; Nicholas C Tonial; Alvin Tieu; Adrien A E RaoPeters; Brad L Urquhart Journal: Pharmacol Res Perspect Date: 2019-04-26
Authors: Sarah M Robertson; Frank Maldarelli; Ven Natarajan; Elizabeth Formentini; Raul M Alfaro; Scott R Penzak Journal: J Acquir Immune Defic Syndr Date: 2008-12-15 Impact factor: 3.771