Evidence map›Paper›PMID 37369955›Full record

ArticleClinical pharmacokinetics2023

Pharmacokinetics, Metabolism, and Excretion of Intravenous [14C]Difelikefalin in Healthy Subjects and Subjects on Hemodialysis.

Jeffrey G Stark, Patrick K Noonan, Robert H Spencer, Sarbani Bhaduri, Stephen J O'Connor, Frédérique Menzaghi

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03947970 (A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Metabolism of [14C] CR845 in Patients With End Stage Renal Disease on Hemodialysis and in Healthy Subjects), which is not on this map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 8% 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.

NCT03947970 phase1completednot on this map

A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Metabolism of [14C] CR845 in Patients With End Stage Renal Disease on Hemodialysis and in Healthy Subjects

TypeinterventionalSponsorCara Therapeutics, Inc.Ran2019 to 2019Enrolled12ConditionsHemodialysis, HealthyArms[14C] CR845
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Pharmacokinetics, Mass Balance and Metabolism of [European journal of drug metabolism and pharmacokinetics · 2023
    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 2 institutions in 1 country.

Jeffrey G StarkWorldwide Clinical Trials, Austin, TX, USA.
Patrick K NoonanCara Therapeutics, Inc., 4 Stamford Plaza, 107 Elm Street, 9th Floor, Stamford, CT, 06902, USA.
Robert H SpencerCara Therapeutics, Inc., 4 Stamford Plaza, 107 Elm Street, 9th Floor, Stamford, CT, 06902, USA. rspencer@caratherapeutics.com.ORCID 0000-0001-6435-9707
Sarbani BhaduriBhaduri Biotech Consulting, El Paso, TX, USA.
Stephen J O'ConnorCara Therapeutics, Inc., 4 Stamford Plaza, 107 Elm Street, 9th Floor, Stamford, CT, 06902, USA.
Frédérique MenzaghiCara Therapeutics, Inc., 4 Stamford Plaza, 107 Elm Street, 9th Floor, Stamford, CT, 06902, USA.
Cara Therapeutics (United States) · USWorldwide Clinical Trials (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveDifelikefalin, a selective kappa-opioid receptor agonist, is the first approved treatment for moderate-to-severe pruritus in patients with end-stage renal disease (ESRD) on hemodialysis (HD) in the USA and Europe. The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [

methodsTwelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [

resultsThe median time to maximum concentration was similar for HD and healthy subjects, occurring at 5 min post-dose. The mean area under the concentration-time curve (AUC) was approximately 11-fold higher in HD versus healthy subjects; mean plasma half-life was 38.0 h and 2.6 h, respectively. In healthy subjects, 80.5% of the dose was recovered in urine, and 11.3% was recovered in feces. In subjects on HD, 58.8% of the dose was recovered in feces, and 19.5% was recovered in dialysate [for subjects on HD with residual kidney function (n = 3), 11.2% was recovered in urine]. Based on plasma AUC

conclusionIn subjects on HD, difelikefalin total exposure was higher and plasma half-life was longer compared with subjects with intact renal function. Metabolism was low in both healthy subjects and subjects on HD, with unchanged drug representing > 99% of systemic circulation; however, the route of excretion was primarily into urine versus feces in healthy subjects, and feces versus dialysate in subjects on HD. REGISTRATION: ClinicalTrials.gov NCT03947970.

Indexed as

Renal DialysisAdultCarbon RadioisotopesHealthy VolunteersHumansMalePiperidinesCarbon-14Carbon RadioisotopesdifelikefalinPiperidines

Identifiers

PMID37369955
PMCPMC10450003
OpenAlexW4382196251

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.