Evidence mapPaperPMID 32064396Full record

ArticleACS omega2020

Preclinical Pharmacokinetics of Complement C5a Receptor Antagonists PMX53 and PMX205 in Mice.

Vinod Kumar, John D Lee, Richard J Clark, Peter G Noakes, Stephen M Taylor, Trent M Woodruff

Open access · goldAbstract read
In one paragraph

Article in ACS omega, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
5.4field-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

52 citing papers in PubMed, 88 citations in OpenAlex.

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  17. Complement System Inhibitory Drugs in a Zebrafish (International journal of molecular sciences · 2023
    Article
  18. Inhibition of C5AR1 impairs osteoclast mobilization and prevents bone loss.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    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

6 authors at 1 institution in 1 country.

Vinod KumarSchool of Biomedical Sciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
John D LeeSchool of Biomedical Sciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
Richard J ClarkSchool of Biomedical Sciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
Peter G NoakesSchool of Biomedical Sciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
Stephen M TaylorSchool of Biomedical Sciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
Trent M WoodruffSchool of Biomedical Sciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia.
The University of Queensland · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The cyclic hexapeptides PMX53 and PMX205 are potent noncompetitive inhibitors of complement C5a receptor 1 (C5aR1). They are widely utilized to study the role of C5aR1 in mouse models, including central nervous system (CNS) disease, and are dosed through a variety of routes of administration. However, a comprehensive pharmacokinetics analysis of these drugs has not been reported. In this study, the blood and CNS pharmacokinetics of PMX53 and PMX205 were performed in mice following intravenous, intraperitoneal, subcutaneous, and oral administration at identical doses. The absorption and distribution of both drugs were rapid and followed a two-compartment model with elimination half-lives of ∼20 min for both compounds. Urinary excretion was the major route of elimination following intravenous dosing with ∼50% of the drug excreted unchanged within the first 12 h. Oral bioavailability of PMX205 was higher than that of PMX53 (23% versus 9%), and PMX205 was also more efficient than PMX53 at entering the intact CNS. In comparison to other routes, subcutaneous administration of PMX205 resulted in high bioavailability (above 90%), as well as prolonged plasma and CNS exposure. Finally, repeated daily oral or subcutaneous administration of PMX205 demonstrated no accumulation of drug in blood, the brain, or the spinal cord, promoting its safety for chronic dosing. These results will be helpful in correlating the desired therapeutic effects of these C5aR1 antagonists with their pharmacokinetic profile. It also suggests that subcutaneous dosing of PMX205 may be an appropriate route of administration for future clinical testing in neurological disease.

Identifiers

PMID32064396
PMCPMC7017397
OpenAlexW3004279507

What Socratic 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 Socratic graph.