Premium
Lopinavir/ritonavir Reduces Bupropion Plasma Concentrations in Healthy Subjects
Author(s) -
Hogeland G W,
Swindells S,
McNabb J C,
Kashuba A D M,
Yee G C,
Lindley C M
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100027
Subject(s) - bupropion , pharmacokinetics , pharmacology , cmax , ritonavir , lopinavir , medicine , drug interaction , active metabolite , human immunodeficiency virus (hiv) , smoking cessation , viral load , disease , family medicine , pathology , covid-19 , antiretroviral therapy , infectious disease (medical specialty)
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) ∞ by 57% (90% CI, 32–83% P <0.01). Hydroxybupropion C max and AUC ∞ 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. Clinical Pharmacology & Therapeutics (2007) 81 , 69–75. doi: 10.1038/sj.clpt.6100027