Evidence map›Paper›PMID 25187485›Full record

Trial reportDrug metabolism and disposition: the biological fate of chemicals2014

Gene variants in CYP2C19 are associated with altered in vivo bupropion pharmacokinetics but not bupropion-assisted smoking cessation outcomes.

Andy Z X Zhu, Qian Zhou, Lisa Sanderson Cox, Jasjit S Ahluwalia, Neal L Benowitz, Rachel F Tyndale

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion.Drug metabolism and disposition: the biological fate of chemicals · 2024
    Trial
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. The Journal of pharmacology and experimental therapeutics · 2022
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Usefulness of Pharmacogenetic Analysis in Psychiatric Clinical Practice: A Case Report.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2018
    Article
  13. Pharmacogenetic Optimization of Smoking Cessation Treatment.Trends in pharmacological sciences · 2017
    Review
  14. Pharmacokinetics of Bupropion and Its Pharmacologically Active Metabolites in Pregnancy.Drug metabolism and disposition: the biological fate of chemicals · 2016
    Article
  15. Article
  16. Article
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 5 institutions in 2 countries.

Andy Z X ZhuDepartments of Pharmacology and Toxicology (A.Z.X.Z., Q.Z., R.F.T.) and Department of Psychiatry (R.F.T.), University of Toronto, Ontario, Canada; Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kansas (L.S.C.); Department of Medicine and Center for Health Equity, University of Minnesota Medical School, Minneapolis, Minnesota (J.S.A.); Division of Clinical Pharmacology and Experimental Therapeutics, Departments of Medicine and Bioengineering & Therapeutic Sciences, University of California, San Francisco, California (N.L.B.); and Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, Ontario, Canada (R.F.T.).
Qian ZhouDepartments of Pharmacology and Toxicology (A.Z.X.Z., Q.Z., R.F.T.) and Department of Psychiatry (R.F.T.), University of Toronto, Ontario, Canada; Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kansas (L.S.C.); Department of Medicine and Center for Health Equity, University of Minnesota Medical School, Minneapolis, Minnesota (J.S.A.); Division of Clinical Pharmacology and Experimental Therapeutics, Departments of Medicine and Bioengineering & Therapeutic Sciences, University of California, San Francisco, California (N.L.B.); and Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, Ontario, Canada (R.F.T.).
Lisa Sanderson CoxDepartments of Pharmacology and Toxicology (A.Z.X.Z., Q.Z., R.F.T.) and Department of Psychiatry (R.F.T.), University of Toronto, Ontario, Canada; Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kansas (L.S.C.); Department of Medicine and Center for Health Equity, University of Minnesota Medical School, Minneapolis, Minnesota (J.S.A.); Division of Clinical Pharmacology and Experimental Therapeutics, Departments of Medicine and Bioengineering & Therapeutic Sciences, University of California, San Francisco, California (N.L.B.); and Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, Ontario, Canada (R.F.T.).
Jasjit S AhluwaliaDepartments of Pharmacology and Toxicology (A.Z.X.Z., Q.Z., R.F.T.) and Department of Psychiatry (R.F.T.), University of Toronto, Ontario, Canada; Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kansas (L.S.C.); Department of Medicine and Center for Health Equity, University of Minnesota Medical School, Minneapolis, Minnesota (J.S.A.); Division of Clinical Pharmacology and Experimental Therapeutics, Departments of Medicine and Bioengineering & Therapeutic Sciences, University of California, San Francisco, California (N.L.B.); and Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, Ontario, Canada (R.F.T.).
Neal L BenowitzDepartments of Pharmacology and Toxicology (A.Z.X.Z., Q.Z., R.F.T.) and Department of Psychiatry (R.F.T.), University of Toronto, Ontario, Canada; Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kansas (L.S.C.); Department of Medicine and Center for Health Equity, University of Minnesota Medical School, Minneapolis, Minnesota (J.S.A.); Division of Clinical Pharmacology and Experimental Therapeutics, Departments of Medicine and Bioengineering & Therapeutic Sciences, University of California, San Francisco, California (N.L.B.); and Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, Ontario, Canada (R.F.T.).
Rachel F TyndaleDepartments of Pharmacology and Toxicology (A.Z.X.Z., Q.Z., R.F.T.) and Department of Psychiatry (R.F.T.), University of Toronto, Ontario, Canada; Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kansas (L.S.C.); Department of Medicine and Center for Health Equity, University of Minnesota Medical School, Minneapolis, Minnesota (J.S.A.); Division of Clinical Pharmacology and Experimental Therapeutics, Departments of Medicine and Bioengineering & Therapeutic Sciences, University of California, San Francisco, California (N.L.B.); and Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, Ontario, Canada (R.F.T.) r.tyndale@utoronto.ca.
University of Kansas · USCentre for Addiction and Mental Health · CAUniversity of California, San Francisco · USUniversity of Minnesota · USUniversity of Toronto · CA

Funding

UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
University of Toronto Coordinating Genetics Core & Clinical Trial SiteU01DA020830 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI TYNDALE, RACHEL FYNVOLA · 2005 to 2014
$22.4M
Research Support CoreP30DA012393 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JACOB, PEYTON, JONES, REESE T. · 1999 to 2024
$17.1M
Helping African American Light Smokers QuitR01CA091912 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI COX, LISA SANDERSON · 2001 to 2010
$5.6M
Safety of Nicotine Reduction StrategyR01CA078603 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BENOWITZ, NEAL L · 1999 to 2009
$4.6M
CIHR MOP86471NCATS NIH HHS UL1 TR000004NCI NIH HHS CA091912NCI NIH HHS CA78603NCI NIH HHS R01 CA078603NCI NIH HHS R01 CA091912NCRR NIH HHS UL1 RR024131NIDA NIH HHS DA020830NIDA NIH HHS DA12393NIDA NIH HHS P30 DA012393NIDA NIH HHS U01 DA020830
6 · The paper itself

Abstract

Bupropion is used clinically to treat depression and to promote smoking cessation. It is metabolized by CYP2B6 to its active metabolite hydroxybupropion, yet alterations in CYP2B6 activity have little impact on bupropion plasma levels. Furthermore, less than 10% of a bupropion dose is excreted as urinary bupropion and its characterized metabolites hydroxybupropion, threohydrobupropion, and erythrohydrobupropion, suggesting that alternative metabolic pathways may exist. In vitro data suggested CYP2C19 could metabolize bupropion. The current study investigated the impact of functional CYP2C19 genetic variants on bupropion pharmacokinetics and treatment outcomes. In 42 healthy volunteers, CYP2C19*2 (a reduced activity allele) was associated with higher bupropion area under the plasma concentration-time curve (AUC), but similar hydroxybupropion AUC. The mean bupropion AUC was 771 versus 670 hours⋅ng/ml in individuals with and without CYP2C19*2, respectively (P = 0.017). CYP2C19*2 was also associated with higher threohydrobupropion and erythrohydrobupropion AUC (P < 0.005). Adjusting for CYP2B6 genotype did not alter these associations, and CYP2C19 variants did not alter the utility of the hydroxybupropion/bupropion ratio as a measure of CYP2B6 activity. Finally, in a clinical trial of 540 smokers, CYP2C19 genotype was not associated with smoking cessation outcomes, supporting the hypothesis that bupropion response is mediated by hydroxybupropion, which is not altered by CYP2C19. In conclusion, our study reports the first in vivo evidence that reduced CYP2C19 activity significantly increases the steady-state exposure to bupropion and its reductive metabolites threohydrobupropion and erythrohydrobupropion. These pharmacokinetic changes were not associated with differences in bupropion's ability to promote smoking cessation in smokers, but may influence the side effects and toxicity associated with bupropion.

Indexed as

Area Under CurveBupropionCytochrome P-450 CYP2C19Double-Blind MethodHealthy VolunteersHumansPlacebosSmoking CessationBupropionCytochrome P-450 CYP2C19Placebos

Identifiers

PMID25187485
PMCPMC4201132
OpenAlexW2160380703

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.