Evidence map›Paper›PMID 25033762›Full record

ArticlePharmaceutical research2015

Quantitative ADME proteomics - CYP and UGT enzymes in the Beagle dog liver and intestine.

Aki T Heikkinen, Arno Friedlein, Mariette Matondo, Oliver J D Hatley, Aleksanteri Petsalo, Risto Juvonen, Aleksandra Galetin, Amin Rostami-Hodjegan, Ruedi Aebersold, Jens Lamerz and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
6.5field-weighted citation impact, top 4% 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

15 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Article
  3. Assessment of cytochrome P450 induction in canine intestinal organoid models.Xenobiotica; the fate of foreign compounds in biological systems · 2024
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Quantifying gut wall metabolism: methodology matters.Biopharmaceutics & drug disposition · 2017
    Article
  12. Article
  13. Review
  14. Review
  15. Review
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

13 authors at 5 institutions in 3 countries.

Aki T HeikkinenSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
Arno Friedlein
Mariette Matondo
Oliver J D Hatley
Aleksanteri Petsalo
Risto Juvonen
Aleksandra Galetin
Amin Rostami-Hodjegan
Ruedi Aebersold
Jens Lamerz
Tom Dunkley
Paul Cutler
Neil Parrott
Roche (Switzerland) · CHUniversity of Eastern Finland · FIETH Zurich · CHSimcyp (United Kingdom) · GBUniversity of Manchester · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeBeagle dogs are used to study oral pharmacokinetics and guide development of drug formulations for human use. Since mechanistic insight into species differences is needed to translate findings in this species to human, abundances of cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) drug metabolizing enzymes have been quantified in dog liver and intestine.

methodsAbundances of enzymes were measured in Beagle dog intestine and liver using selected reaction monitoring mass spectrometry.

resultsSeven and two CYPs were present in the liver and intestine, respectively. CYP3A12 was the most abundant CYP in both tissues. Seven UGT enzymes were quantified in the liver and seven in the intestine although UGT1A11 and UGT1A9 were present only in the intestine and UGT1A7 and UGT2B31 were found only in the liver. UGT1A11 and UGT1A2 were the most abundant UGTs in the intestine and UGT2B31 was the most abundant UGT in the liver. Summed abundance of UGT enzymes was similar to the sum of CYP enzymes in the liver whereas intestinal UGTs were up to four times more abundant than CYPs. The estimated coefficients of variation of abundance estimates in the livers of 14 donors were separated into biological and technical components which ranged from 14 to 49% and 20 to 39%, respectively.

conclusionsAbundances of canine CYP enzymes in liver and intestine have been confirmed in a larger number of dogs and UGT abundances have been quantified for the first time. The biological variability in hepatic CYPs and UGTs has also been estimated.

Indexed as

AnimalsColonCytochrome P-450 Enzyme SystemDogsFemaleGlucuronosyltransferaseHumansIntestine, SmallLiverMaleMass SpectrometryMicrosomesModels, BiologicalProteomicsSpecies SpecificityCytochrome P-450 Enzyme SystemGlucuronosyltransferase

Identifiers

PMID25033762
OpenAlexW2005123904

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.