Evidence map›Paper›PMID 37306899›Full record

ArticleClinical pharmacokinetics2023

A Joint Pharmacokinetic Model for the Simultaneous Description of Plasma and Whole Blood Tacrolimus Concentrations in Kidney and Lung Transplant Recipients.

Jeroen V Koomen, Tim J Knobbe, Tanja R Zijp, Daan Kremer, C Tji Gan, Erik A M Verschuuren, Stephan J L Bakker, Daan J Touw, Pieter J Colin, TransplantLines Investigators

Open access · hybridAbstract read
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. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 10% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
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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

10 authors at 1 institution in 1 country.

Jeroen V KoomenDepartment of Anaesthesiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. j.v.koomen@umcg.nl.ORCID http://orcid.org/0000-0001-7253-3998
Tim J KnobbeDivision of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Tanja R ZijpDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Daan KremerDivision of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
C Tji GanDepartment of Respiratory Diseases and Lung Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Erik A M VerschuurenDepartment of Respiratory Diseases and Lung Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Stephan J L BakkerDivision of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Daan J TouwDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Pieter J ColinDepartment of Anaesthesiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
TransplantLines Investigators
University Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveHistorically, dosing of tacrolimus is guided by therapeutic drug monitoring (TDM) of the whole blood concentration, which is strongly influenced by haematocrit. The therapeutic and adverse effects are however expected to be driven by the unbound exposure, which could be better represented by measuring plasma concentrations.

objectiveWe aimed to establish plasma concentration ranges reflecting whole blood concentrations within currently used target ranges.

methodsPlasma and whole blood tacrolimus concentrations were determined in samples of transplant recipients included in the TransplantLines Biobank and Cohort Study. Targeted whole blood trough concentrations are 4-6 ng/mL and 7-10 ng/mL for kidney and lung transplant recipients, respectively. A population pharmacokinetic model was developed using non-linear mixed-effects modelling. Simulations were performed to infer plasma concentration ranges corresponding to whole blood target ranges.

resultsPlasma (n = 1973) and whole blood (n = 1961) tacrolimus concentrations were determined in 1060 transplant recipients. A one-compartment model with fixed first-order absorption and estimated first-order elimination characterised observed plasma concentrations. Plasma was linked to whole blood using a saturable binding equation (maximum binding 35.7 ng/mL, 95% confidence interval (CI) 31.0-40.4 ng/mL; dissociation constant 0.24 ng/mL, 95% CI 0.19-0.29 ng/mL). Model simulations indicate that patients within the whole blood target range are expected to have plasma concentrations (95% prediction interval) of 0.06-0.26 ng/mL and 0.10-0.93 ng/mL for kidney and lung transplant recipients, respectively.

conclusionWhole blood tacrolimus target ranges, currently used to guide TDM, were translated to plasma concentration ranges of 0.06-0.26 ng/mL and 0.10-0.93 ng/mL for kidney and lung transplant recipients, respectively.

Indexed as

Immunosuppressive AgentsTacrolimusCohort StudiesHumansKidneyLungTransplant RecipientsImmunosuppressive AgentsTacrolimus

Identifiers

PMID37306899
PMCPMC10386913
OpenAlexW4380291182

What OpenQuestion holds

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Registered trials

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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.