Effect of renal impairment on the pharmacokinetics of bupropion and its metabolites.
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.
Turpeinen
Miia
M
Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland. miia.turpeinen@oulu.fi
Koivuviita
Niina
N
Tolonen
Ari
A
Reponen
Petri
P
Lundgren
Stefan
S
Miettunen
Jouko
J
Metsärinne
Kaj
K
Rane
Anders
A
Pelkonen
Olavi
O
Laine
Kari
K
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
D018687:Antidepressive Agents, Second-Generation; D016642:Bupropion; D003577:Cytochrome P-450 Enzyme System