Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects.
Limited data are available about the effect of steady-state lopinavir and ritonavir (LPV/r) on bupropion pharmacokinetics. As patients may benefit by using these two agents in combination, this study determined the extent and direction of this drug-drug interaction. Twelve healthy volunteers received a single 100 mg dose of sustained-release bupropion before and after 2 weeks of treatment with LPV/r 400 mg/100 mg twice daily. Pharmacokinetics profiles were determined on days 1 and 30 for bupropion and hydroxybupropion and days 29 and 30 for LPV/r. LPV/r administration significantly decreased bupropion maximum plasma concentration (C(max)) by 57% (90% confidence interval (CI), 38-76%; P<0.01) and area under the curve (AUC) infinity by 57% (90% CI, 32-83%; P<0.01). Hydroxybupropion C(max) and AUC infinity decreased by 31% (90% CI, 7-55%; P<0.01) and by 50% (90% CI, 34-65%; P<0.01), respectively. No significant changes in the pharmacokinetics of LPV/r were found following administration of a single dose of bupropion. Concurrent use of LPV/r and bupropion resulted in decreased exposure to bupropion and its active metabolite hydroxybupropion that may necessitate as much as a 100% dose increase of bupropion. A probable mechanism for this interaction is the concurrent induction of cytochrome P450 2B6 and UDP-glucuronosyltransferase enzymes. LPV/r exposure is unaffected by a single dose of bupropion.
Hogeland
G W
GW
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina School of Pharmacy, Chapel Hill, North Carolina, USA.
Swindells
S
S
McNabb
J C
JC
Kashuba
A D M
AD
Yee
G C
GC
Lindley
C M
CM
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016642:Bupropion / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D004336:Drug Antagonism; D004338:Drug Combinations; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D061466:Lopinavir; D008297:Male; D008657:Metabolic Clearance Rate; D011744:Pyrimidinones / Q000008:administration & dosage / Q000494:pharmacology*; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D016642:Bupropion; D061466:Lopinavir; D019438:Ritonavir; C496215:radafaxine