Evidence map›Paper›PMID 24623479›Full record

ArticlePharmaceutical research2014

Reduced physiologically-based pharmacokinetic model of repaglinide: impact of OATP1B1 and CYP2C8 genotype and source of in vitro data on the prediction of drug-drug interaction risk.

Michael Gertz, Nikolaos Tsamandouras, Carolina Säll, J Brian Houston, Aleksandra Galetin

Abstract read
PubMed Publisher
In one paragraph

Article in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
6.9field-weighted citation impact, top 3% 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

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Leveraging human genetic and adverse outcome pathway (AOP) data to inform susceptibility in human health risk assessment.Mammalian genome : official journal of the International Mammalian Genome Society · 2018
    Article
  20. The Promises of Quantitative Proteomics in Precision Medicine.Journal of pharmaceutical sciences · 2017
    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

5 authors at 2 institutions in 2 countries.

Michael GertzCentre for Applied Pharmacokinetic Research Manchester Pharmacy School, The University of Manchester, Oxford Road, M13 9PT, Manchester, UK.
Nikolaos Tsamandouras
Carolina Säll
J Brian Houston
Aleksandra Galetin
University of Manchester · GBRoche (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTo investigate the effect of OATP1B1 genotype as a covariate on repaglinide pharmacokinetics and drug-drug interaction (DDIs) risk using a reduced physiologically-based pharmacokinetic (PBPK) model.

methodsTwenty nine mean plasma concentration-time profiles for SLCO1B1 c.521T>C were used to estimate hepatic uptake clearance (CLuptake) in different genotype groups applying a population approach in NONMEM v.7.2.

resultsEstimated repaglinide CLuptake corresponded to 217 and 113 μL/min/10(6) cells for SLCO1B1 c.521TT/TC and CC, respectively. A significant effect of OATP1B1 genotype was seen on CLuptake (48% reduction for CC relative to wild type). Sensitivity analysis highlighted the impact of CLmet and CLdiff uncertainty on the CLuptake optimization using plasma data. Propagation of this uncertainty had a marginal effect on the prediction of repaglinide OATP1B1-mediated DDI with cyclosporine; however, sensitivity of the predicted magnitude of repaglinide metabolic DDI was high. In addition, the reduced PBPK model was used to assess the effect of both CYP2C8*3 and SLCO1B1 c.521T>C on repaglinide exposure by simulations; power calculations were performed to guide prospective DDI and pharmacogenetic studies.

conclusionsThe application of reduced PBPK model for parameter optimization and limitations of this process associated with the use of plasma rather than tissue profiles are illustrated.

Indexed as

CarbamatesComputer SimulationCytochrome P-450 CYP2C8Drug InteractionsGenotypeHumansHypoglycemic AgentsLiver-Specific Organic Anion Transporter 1Models, BiologicalMonte Carlo MethodOrganic Anion TransportersPiperidinesPolymorphism, GeneticProspective StudiesCarbamatesCytochrome P-450 CYP2C8Hypoglycemic AgentsLiver-Specific Organic Anion Transporter 1Organic Anion TransportersPiperidinesrepaglinideSLCO1B1 protein, human

Identifiers

PMID24623479
OpenAlexW2104239473

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.