Evidence map›Paper›PMID 34443621›Full record

ArticleMolecules (Basel, Switzerland)2021

Species Differences in Metabolism of Soluble Epoxide Hydrolase Inhibitor, EC1728, Highlight the Importance of Clinically Relevant Screening Mechanisms in Drug Development.

Cindy B McReynolds, Jun Yang, Alonso Guedes, Christophe Morisseau, Roberto Garcia, Heather Knych, Caitlin Tearney, Briana Hamamoto, Sung Hee Hwang, Karen Wagner and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecules (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

11 authors.

Cindy B McReynoldsUC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA.
Jun YangUC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA.
Alonso GuedesDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.ORCID 0000-0002-7980-9018
Christophe MorisseauUC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA.
Roberto GarciaDechra Development LLC, 1 Monument Sq, Portland, ME 04101, USA.
Heather KnychK.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
Caitlin TearneyDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.
Briana HamamotoK.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
Sung Hee HwangUC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA.
Karen WagnerUC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA.
Bruce D HammockUC Davis Comprehensive Cancer Center, Department of Entomology and Nematology, University of California, Davis, Davis, CA 95616, USA.ORCID 0000-0003-1408-8317

Funding

Workshop on Environmental Technology Transfer and EntrepreneurshipP42ES004699 · NIEHS · UNIVERSITY OF CALIFORNIA DAVIS · PI HAMMOCK, BRUCE D · 1987 to 2021
$50.1M
Supplement for bioactive lipids as effectors and indicators of the deleterious effects of human healthR35ES030443 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MORISSEAU, CHRISTOPHE HP · 2019 to 2025
$5.8M
UC Davis Training Program in Chemical BiologyT32GM113770 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BEAL, PETER A. · 2015 to 2019
$742k
Center for Companion Animal Health, University of California, Davis To A.G. for dog PK studiesNIEHS NIH HHS P42 ES004699NIEHS NIH HHS R35 ES030443NIH HHS R35 ES030443NIH HHS T32 GM113770Winn Feline Foundation Every Cat Health Foundation (to A.G. for 1 mg/kg IV cat studies)
6 · The paper itself

Abstract

There are few novel therapeutic options available for companion animals, and medications rely heavily on repurposed drugs developed for other species. Considering the diversity of species and breeds in companion animal medicine, comprehensive PK exposures in the companion animal patient is often lacking. The purpose of this paper was to assess the pharmacokinetics after oral and intravenous dosing in domesticated animal species (dogs, cats, and horses) of a novel soluble epoxide hydrolase inhibitor, EC1728, being developed for the treatment of pain in animals. Results: Intravenous and oral administration revealed that bioavailability was similar for dogs, and horses (42 and 50% F) but lower in mice and cats (34 and 8%, respectively). Additionally, clearance was similar between cats and mice, but >2× faster in cats vs. dogs and horses. Efficacy with EC1728 has been demonstrated in mice, dogs, and horses, and despite the rapid clearance of EC1728 in cats, analgesic efficacy was demonstrated in an acute pain model after intravenous but not oral dosing. Conclusion: These results demonstrate that exposures across species can vary, and investigation of therapeutic exposures in target species is needed to provide adequate care that addresses efficacy and avoids toxicity.

Indexed as

Enzyme InhibitorsEpoxide HydrolasesSpecies SpecificityAdministration, IntravenousAdministration, OralAnimalsBiological AvailabilityCatsDogsDrug DevelopmentFemaleHorsesMaleMiceEnzyme InhibitorsEpoxide Hydrolasescompanion animalsfeline drug metabolismpharmacokineticssoluble epoxide hydrolase

Identifiers

PMID34443621
PMCPMC8399023

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.