Evidence map›Paper›PMID 38722350›Full record

Trial reportEuropean journal of clinical pharmacology2024

Assessment of body mass-related covariates for rifampicin pharmacokinetics in healthy Caucasian volunteers.

Muhammad Bilal, Sami Ullah, Ulrich Jaehde, Christina Trueck, Dario Zaremba, Bertil Wachall, Manfred Wargenau, Bernhard Scheidel, Martin H J Wiesen, Malaz Gazzaz and 5 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Muhammad BilalDepartment I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. muhammad.bilal@uk-koeln.de.
Sami UllahDepartment I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Ulrich JaehdeDepartment of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, Bonn, Germany.
Christina TrueckDepartment I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Dario ZarembaDepartment I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Bertil WachallInfectoPharm Arzneimittel Und Consilium GmbH, 64646, Heppenheim, Germany.
Manfred WargenauM.A.R.C.O. GmbH & Co. KG, Dusseldorf, Germany.
Bernhard ScheidelACC GmbH Analytical Clinical Concepts, Leidersbach, Germany.
Martin H J WiesenPharmacology at the Laboratory Diagnostics Centre, Faculty of Medicine, University Hospital Cologne, University of Cologne, Therapeutic Drug Monitoring, Cologne, Germany.
Malaz GazzazPharmaceutical Practices Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
Chunli ChenDepartment I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Sören BüskerDepartment I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Uwe FuhrDepartment I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Max TaubertDepartment I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Charalambos DokosDepartment I of Pharmacology, Center for Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Funding

2022 ESI International High Impact Research Article Cooperation Program 212-54900112International Postdoctoral Exchange Fellowship Program from the Office of China Postdoctoral Council 2020106 & PC2020013the National Natural Science Foundation of Heilongjiang Province YQ2022C017
6 · The paper itself

Abstract

purposeCurrently, body weight-based dosing of rifampicin is recommended. But lately, fat-free mass (FFM) was reported to be superior to body weight (BW). The present evaluation aimed to assess the influence of body mass-related covariates on rifampicin's pharmacokinetics (PK) parameters in more detail using non-linear mixed effects modeling (NLMEM).

methodsTwenty-four healthy Caucasian volunteers were enrolled in a bioequivalence study, each receiving a test and a reference tablet of 600 mg of rifampicin separated by a wash-out period of at least 9 days. Monolix version 2023R1 was used for NLMEM. Monte Carlo simulations (MCS) were performed to visualize the relationship of body size descriptors to the exposure to rifampicin.

resultsA one-compartment model with nonlinear (Michaelis-Menten) elimination and zero-order absorption kinetics with a lag time best described the data. The covariate model including fat-free mass (FFM) on volume of distribution (V/F) and on maximum elimination rate (Vmax/F) lowered the objective function value (OFV) by 56.4. The second-best covariate model of sex on V/F and Vmax/F and BW on V/F reduced the OFV by 51.2. The decrease in unexplained inter-individual variability on Vmax/F in both covariate models was similar. For a given dose, MCS showed lower exposure to rifampicin with higher FFM and accordingly in males compared to females with the same BW and body height.

conclusionOur results indicate that beyond BW, body composition as reflected by FFM could also be relevant for optimized dosing of rifampicin. This assumption needs to be studied further in patients treated with rifampicin.

Indexed as

Healthy VolunteersModels, BiologicalRifampinWhite PeopleAdultAntibiotics, AntitubercularBody WeightCross-Over StudiesFemaleHumansMaleMonte Carlo MethodNonlinear DynamicsTherapeutic EquivalencyYoung AdultAntibiotics, AntitubercularRifampinBody weightCovariate modelingFat-free massPopulation pharmacokineticsRifampicin

Identifiers

PMID38722350
PMCPMC11303472

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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.