Dose‐Related Reduction in Bupropion Plasma Concentrations by Ritonavir

Park, Joo Hyun; Vousden, Marika; Brittain, Clare; McConn, Donavon J.; Iavarone, Laura; Ascher, John; Sutherland, Suzanne M.; Muir, Keith T.

doi:10.1177/0091270009359524

Cited by 36 publications

(16 citation statements)

References 17 publications

(21 reference statements)

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“…increased 4-OH BUP Cl form (2.1-fold) and decreased BUP AUC 33% . RTV has been shown to cause a dose-dependent decrease in BUP AUC (66 and 22% for 600 and 100 mg b.i.d., respectively) (Park et al, 2010). The reason we did not observe a statistically significant decrease in BUP AUC is unclear.…”

Section: Discussionmentioning

confidence: 62%

Complex Drug Interactions of HIV Protease Inhibitors 2: In Vivo Induction and In Vitro to In Vivo Correlation of Induction of Cytochrome P450 1A2, 2B6, and 2C9 by Ritonavir or Nelfinavir

Kirby¹,

Collier²,

Kharasch³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Drug-drug interactions (DDIs) with the HIV protease inhibitors (PIs) are complex, paradoxical (e.g., ritonavir/alprazolam), and involve multiple mechanisms. As part of a larger study to better understand these DDIs and to devise a framework for in vitro to in vivo prediction of these DDIs, we determined the inductive effect of ϳ2 weeks of administration of two prototypic PIs, nelfinavir (NFV), ritonavir (RTV), and rifampin (RIF; induction positive control) on the cytochrome P450 enzymes CYP1A2, CYP2B6, CYP2C9, and CYP2D6 and the inductive or inductive plus inhibitory effect of NFV, RTV, or RIF on CYP3A and P-glycoprotein in healthy human volunteers. Statistically significant induction of CYP1A2 (2.1-, 2.9-, and 2.2-fold), CYP2B6 (1.8-, 2.4-, and 4-fold), and CYP2C9 (1.3-, 1.8-, and 2.6-fold) was observed after NFV, RTV, or RIF treatment, respectively (as expected, CYP2D6 was not induced). Moreover, we accurately predicted the in vivo induction of these enzymes by quantifying their induction by the PIs in human hepatocytes and by using RIF as an in vitro to in vivo scalar. On the basis of the modest in vivo induction of CYP1A2, CYP2B6, or CYP2C9, the in vivo paradoxical DDIs with the PIs are likely explained by mechanisms other than induction of these enzymes such as induction of other metabolic enzymes, transporters, or both.

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Section: Discussionmentioning

confidence: 62%

Complex Drug Interactions of HIV Protease Inhibitors 2: In Vivo Induction and In Vitro to In Vivo Correlation of Induction of Cytochrome P450 1A2, 2B6, and 2C9 by Ritonavir or Nelfinavir

Kirby¹,

Collier²,

Kharasch³

et al. 2011

Drug Metab Dispos

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“…57 Subsequent research has demonstrated that the pharmacokinetic clearance of bupropion is pronounced at exposure to high doses of ritonavir (600 mg twice daily), and substantially less so at lower doses, possibly requiring adjustments of bupropion dose (100 mg twice daily). 58 Further, the protease inhibitor combination of lopinavir and ritonavir (400/100 mg) was found to decrease bupropion maximum plasma concentration by 57% with similar reductions in hydroxybupropion concentrations among healthy volunteers. 59 Similarly, there is evidence that efavirenz can result in decreased bupropion plasma concentrations; however, the clinical implications remain unclear.…”

Section: Medication Treatmentsmentioning

confidence: 80%

Smoking Cessation for People Living With HIV/AIDS: A Literature Review and Synthesis

Ledgerwood

Yskes

2016

NICTOB

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Introduction: People living with HIV/AIDS (PLWHA) are more likely to smoke cigarettes than are individuals in the general population. The health implications of tobacco use are substantially more dire among PLWHA than among otherwise healthy smokers, including higher rates of various cancers, cardiovascular disease, inflammation, and lung infections. Efficacious behavioral and medication treatments for treating nicotine dependence have rarely been investigated in PLWHA. Methods: We present a review of studies examining the efficacy of smoking cessation interventions. Results and Conclusions:The literature reveals some limited evidence for the efficacy of behavioral interventions. However, the research literature on these interventions is sparse and the efficacy findings are mixed. Studies exploring the use of mobile technologies for reducing treatment barriers are becoming more prevalent. Few published trials have directly examined the efficacy of pharmacological smoking cessation interventions among PLWHA. Specific gaps in the treatment literature are discussed in detail, and a strategy is presented for developing a greater understanding of factors that contribute to the efficacy of smoking cessation among PLWHA. Implications: This paper provides the most comprehensive review to date on smoking cessation intervention research conducted with PLWHA. It also discusses specific gaps in the literature that should be a priority for future research.

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“…Pharmacokinetic data are limited with respect to interactions with antiretrovirals; however, ritonavir and other boosted protease inhibitors have been shown to reduce the area under the curve for bupropion and sertraline by up to 50%-60% through induction of CYP2B6. [59][60][61] The boosted protease inhibitors fosamprenavir and darunavir have also been shown, in studies of healthy volunteers, to reduce the area under the curve for paroxetine by about 40%-60%; however, the mechanism for this interaction is unclear, as paroxetine is primarily a substrate of CYP2D6. 61,62 Serotonin syndrome was reported in a case series of patients receiving fluoxetine (a CYP2D6 substrate) in conjunction with high-dose (200-600 mg twice daily) ritonavir-based combination antiretroviral therapy.…”

Section: Metabolism: Other Cyp450 Isoenzymesmentioning

confidence: 99%