Evidence map›Paper›PMID 26376650›Full record

Trial reportEuropean journal of clinical pharmacology2015

Stereoselective handling of perhexiline: implications regarding accumulation within the human myocardium.

Cher-Rin Chong, Nigel E Drury, Giovanni Licari, Michael P Frenneaux, John D Horowitz, Domenico Pagano, Benedetta C Sallustio

Abstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

4 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Stereoselectivity of Electron and Energy Transfer in the Quenching of (International journal of molecular sciences · 2020
    Article
  4. 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

7 authors at 5 institutions in 2 countries.

Cher-Rin ChongCardiology and Clinical Pharmacology Departments, Basil Hetzel Institute, Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
Nigel E DruryCardiology and Clinical Pharmacology Departments, Basil Hetzel Institute, Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
Giovanni LicariCardiology and Clinical Pharmacology Departments, Basil Hetzel Institute, Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
Michael P FrenneauxNorwich Medical School, University of East Anglia, Norwich, UK.
John D HorowitzCardiology and Clinical Pharmacology Departments, Basil Hetzel Institute, Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
Domenico PaganoDepartment of Cardiothoracic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
Benedetta C SallustioCardiology and Clinical Pharmacology Departments, Basil Hetzel Institute, Queen Elizabeth Hospital, Woodville South, South Australia, Australia. benedetta.sallustio@health.sa.gov.au.
University of Adelaide · AUBasil Hetzel Institute · AUQueen Elizabeth Hospital Birmingham · GBUniversity of Birmingham · GBUniversity of East Anglia · GB

Funding

British Heart Foundation PG/06/044/20703Wellcome Trust
6 · The paper itself

Abstract

purposePerhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium.

methodPatients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses.

resultsMyocardial uptake of both (+) and (-) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (-) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (-) perhexiline were the plasma concentrations [(+) perhexiline: β = -0.256, p = 0.015; (-) perhexiline: β = -0.347, p = 0.001] and patients' age [(+) perhexiline: β = 0.300, p = 0.004; (-) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (-) perhexiline varied inversely with simultaneous heart rate (β = -0.240, p = 0.015).

conclusion(1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (-) perhexiline may selectively modulate heart rate reduction.

Indexed as

Administration, OralAgedCardiovascular AgentsHeart AtriaHeart VentriclesHumansMiddle AgedMyocardiumPerhexilineStereoisomerismTissue DistributionCardiovascular AgentsPerhexilineDrug uptakeMetabolismPerhexilinePharmacokineticsStereoselectivity

Identifiers

PMID26376650
OpenAlexW1907217385

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.