Evidence map›Paper›PMID 27799204›Full record

Trial reportAntimicrobial agents and chemotherapy2017

Population Pharmacokinetic Modeling To Estimate the Contributions of Genetic and Nongenetic Factors to Efavirenz Disposition.

Jason D Robarge, Ingrid F Metzger, Jessica Lu, Nancy Thong, Todd C Skaar, Zeruesenay Desta, Robert R Bies

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00668395 (Effects of CYP2B6 Genetic Polymorphisms on Efavirenz Pharmacokinetics, Autoinduction and Drug Interactions in Healthy Volunteers.), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% 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.

NCT00668395 nacompletednot on this map

Effects of CYP2B6 Genetic Polymorphisms on Efavirenz Pharmacokinetics, Autoinduction and Drug Interactions in Healthy Volunteers.

TypeinterventionalSponsorIndiana UniversityRan2007 to 2010Enrolled73ConditionsHIVArmsEfavirenz
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Guideline
  2. Trial
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Article
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  9. Article
  10. The Journal of pharmacology and experimental therapeutics · 2022
    Article
  11. Review
  12. Article
  13. Article
  14. Circulating miRNAs as Biomarkers for CYP2B6 Enzyme Activity.Clinical pharmacology and therapeutics · 2021
    Article
  15. Efavirenz Metabolism: Influence of Polymorphic CYP2B6 Variants and Stereochemistry.Drug metabolism and disposition: the biological fate of chemicals · 2019
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

7 authors at 2 institutions in 1 country.

Jason D RobargeIndiana University School of Medicine, Division of Clinical Pharmacology, Indianapolis, Indiana, USA.
Ingrid F MetzgerIndiana University School of Medicine, Division of Clinical Pharmacology, Indianapolis, Indiana, USA.
Jessica LuIndiana University School of Medicine, Division of Clinical Pharmacology, Indianapolis, Indiana, USA.
Nancy ThongIndiana University School of Medicine, Division of Clinical Pharmacology, Indianapolis, Indiana, USA.
Todd C SkaarIndiana University School of Medicine, Division of Clinical Pharmacology, Indianapolis, Indiana, USA.
Zeruesenay DestaIndiana University School of Medicine, Division of Clinical Pharmacology, Indianapolis, Indiana, USA zdesta@iu.edu.
Robert R BiesIndiana University School of Medicine, Division of Clinical Pharmacology, Indianapolis, Indiana, USA.
Indiana University School of MedicineIndiana University – Purdue University Indianapolis · US

Funding

ZOSUQUIDAR TRIHYDROCHLORIDE DURING CONVENTIONAL INDUCTION AND POST-REMISSIONM01RR000750 · NCRR · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI STORNIOLO, ANNA · 1985 to 2008
$25.5M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
Indiana University Comprehensive Training in Clinical PharmacologyT32GM008425 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Zeruesenay Desta, Michael Thomas Eadon · 1992 to 2026
$7.7M
CYP2B6 Genetic Variations and Drug InteractionsR01GM078501 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI DESTA, ZERUESENAY · 2007 to 2015
$3.2M
Prediction of Drug-Drug InteractionsR56GM067308 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI DESTA, ZERUESENAY · 2007 to 2007
$303k
NCATS NIH HHS UL1 TR001108NCRR NIH HHS M01 RR000750NIGMS NIH HHS R01 GM078501NIGMS NIH HHS R56 GM067308NIGMS NIH HHS T32 GM008425
6 · The paper itself

Abstract

Efavirenz pharmacokinetics is characterized by large between-subject variability, which determines both therapeutic response and adverse effects. Some of the variability in efavirenz pharmacokinetics has been attributed to genetic variability in cytochrome P450 genes that alter efavirenz metabolism, such as CYP2B6 and CYP2A6 While the effects of additional patient factors have been studied, such as sex, weight, and body mass index, the extent to which they contribute to variability in efavirenz exposure is inconsistently reported. The aim of this analysis was to develop a pharmacometric model to quantify the contribution of genetic and nongenetic factors to efavirenz pharmacokinetics. A population-based pharmacokinetic model was developed using 1,132 plasma efavirenz concentrations obtained from 73 HIV-seronegative volunteers administered a single oral dose of 600 mg efavirenz. A two-compartment structural model with absorption occurring by zero- and first-order processes described the data. Allometric scaling adequately described the relationship between fat-free mass and apparent oral clearance, as well as fat mass and apparent peripheral volume of distribution. Inclusion of fat-free mass and fat mass in the model mechanistically accounted for correlation between these disposition parameters and sex, weight, and body mass index. Apparent oral clearance of efavirenz was reduced by 25% and 51% in subjects predicted to have intermediate and slow CYP2B6 metabolizer status, respectively. The final pharmacokinetic model accounting for fat-free mass, fat mass, and CYP2B6 metabolizer status was consistent with known mechanisms of efavirenz disposition, efavirenz physiochemical properties, and pharmacokinetic theory. (This study has been registered at ClinicalTrials.gov under identifier NCT00668395.).

Indexed as

Models, StatisticalAdipose TissueAdministration, OralAdolescentAdultAlkynesAnti-HIV AgentsBenzoxazinesBiotransformationBody Mass IndexBody WeightCyclopropanesCytochrome P-450 CYP2A6Cytochrome P-450 CYP2B6Drug Administration ScheduleFemaleAlkynesAnti-HIV AgentsBenzoxazinesCyclopropanesCYP2A6 protein, humanCYP2B6 protein, humanCytochrome P-450 CYP2A6Cytochrome P-450 CYP2B6efavirenzbody compositioncytochrome P450 2B6 (CYP2B6)efavirenzpopulation pharmacokinetics

Identifiers

PMID27799204
PMCPMC5192152
OpenAlexW2545774381

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.