Evidence map›Paper›PMID 23982262›Full record

ArticlePharmacogenetics and genomics2013

Measuring the overall genetic component of nevirapine pharmacokinetics and the role of selected polymorphisms: towards addressing the missing heritability in pharmacogenetic phenotypes?

Janine E Micheli, Leslie W Chinn, Sarah B Shugarts, Ashish Patel, Jeffrey N Martin, David R Bangsberg, Deanna L Kroetz

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmacogenetics and genomics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

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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

7 authors at 2 institutions in 4 countries.

Janine E MicheliDepartments of aBioengineering and Therapeutic Sciences bEpidemiology cMedicine dThe Institute for Human Genetics, University of California, San Francisco, California eRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Massachusetts General Hospital Center for Global Health, Harvard Medical School, Boston, Massachusetts, USA.
Leslie W Chinn
Sarah B Shugarts
Ashish Patel
Jeffrey N Martin
David R Bangsberg
Deanna L Kroetz
PharmacoGenetics (China) · CNWested · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MALLORY O JOHNSON · 1988 to 2026
$93.6M
UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Y. Chen · 1986 to 2026
$30.7M
PHARMACOGENETICS OF MEMBRANE TRANSPORTERSU01GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIACOMINI, KATHLEEN M · 2000 to 2009
$29.2M
TB PREVENTION AND HIV IN THE HOMELESS--AN INTERVENTIONR01MH054907 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BANGSBERG, DAVID ROY · 1995 to 2014
$20.7M
Pharmacogenomics of Membrane TransportersU19GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YEE, SOOK WAH · 2010 to 2014
$16.3M
PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
NIAID NIH HHS P30 AI027763NIDDK NIH HHS P30 DK026743NIGMS NIH HHS GM61390NIGMS NIH HHS T32 GM007175NIGMS NIH HHS U01 GM061390NIGMS NIH HHS U19 GM061390NIMH NIH HHS MH54907NIMH NIH HHS R01 MH054907
6 · The paper itself

Abstract

objectiveNevirapine is an important component of highly active antiretroviral therapy used in the treatment of HIV infection. There is a considerable variation in the pharmacokinetics of nevirapine and this variation can impact the efficacy and toxicity of nevirapine. Although some of this variation can be attributed to environmental factors, the degree to which heritability influences nevirapine pharmacokinetics is unknown. This study aims to estimate how much variation in nevirapine pharmacokinetics is due to genetic factors and to investigate the contribution of selected polymorphisms to this variability.

methodsTwo doses of immediate-release nevirapine were administered to European (n=11) and African American (n=6) participants recruited from the Research in Access to Care in the Homeless cohort. A repeated drug administration method was then used to determine the relative genetic contribution (r(GC)) to variability in nevirapine AUC(0-6 h). Nevirapine plasma levels were quantified using LC/MS/MS. Patients were also genotyped for selected polymorphisms in candidate genes that may influence nevirapine pharmacokinetics.

resultsA significant r(GC) for nevirapine AUC(0-6 h) was found in Europeans (P=0.02) and African Americans (P=0.01). A trend toward higher nevirapine AUC(0-6 h) for the CYP2B6 516TT (rs3745274; Q172H) genotype was observed in European Americans (P=0.19).

conclusionThis study demonstrates that there is a significant genetic component to variability in nevirapine pharmacokinetics. Although genetic variants such as CYP2B6 polymorphisms attributed to some of this variation, these data suggest that there may be additional genetic factors that influence nevirapine pharmacokinetics.

Indexed as

AdultAgedAnti-HIV AgentsAryl Hydrocarbon HydroxylasesATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Black or African AmericanCytochrome P-450 CYP2B6FemaleGenetic VariationGenotypeHIV InfectionsHumansMaleMiddle AgedNevirapineABCB1 protein, humanAnti-HIV AgentsAryl Hydrocarbon HydroxylasesATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1CYP2B6 protein, humanCytochrome P-450 CYP2B6Nevirapine

Identifiers

PMID23982262
PMCPMC4048019
OpenAlexW2028231662

What OpenQuestion holds

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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.