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Dose optimisation of first-line tuberculosis drugs using therapeutic drug monitoring in saliva: feasible for rifampicin, not for isoniazid

Simone H.J. van den Elsen, Onno W. Akkerman, Mireille Wessels, Erwin M. Jongedijk, Samiksha Ghimire, Tjip S. van der Werf, Mathieu S. Bolhuis, Daan J. Touw, Jan-Willem C. Alffenaar
European Respiratory Journal 2020 56: 2000803; DOI: 10.1183/13993003.00803-2020
Simone H.J. van den Elsen
1University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
2Hospital Group Twente, Dept of Clinical Pharmacy, Almelo and Hengelo, The Netherlands
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Onno W. Akkerman
3University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord, Haren, The Netherlands
4University of Groningen, University Medical Center Groningen, Dept of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands
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Mireille Wessels
1University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
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Erwin M. Jongedijk
1University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
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Samiksha Ghimire
1University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
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Tjip S. van der Werf
4University of Groningen, University Medical Center Groningen, Dept of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands
5University of Groningen, University Medical Center Groningen, Dept of Internal Medicine, Groningen, The Netherlands
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Mathieu S. Bolhuis
1University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
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Daan J. Touw
1University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
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Jan-Willem C. Alffenaar
1University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
6Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
7Westmead Hospital, Sydney, Australia
8Marie Bashir Institute of Infectious Diseases and Biosecurity, Sydney, Australia
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Extract

The persisting worldwide burden of tuberculosis (TB) is worrisome. In 2018, an estimated 10 million individuals developed TB and 1.45 million infected individuals died [1]. The increase in drug resistance is an important point of concern. Resistance can be acquired by inappropriate drug management, noncompliance and insufficient drug exposure [2, 3]. The last is frequently described for the first-line TB drugs rifampicin and isoniazid due to large interindividual pharmacokinetic variability [3]. Therapeutic drug monitoring (TDM) can be used to verify drug exposure and adjust individual drug dosages if needed [4].

Abstract

Therapeutic drug monitoring using saliva samples is feasible for rifampicin, despite low penetration, but is not feasible for isoniazid, which showed inexplicable highly variable saliva/serum concentration ratios https://bit.ly/2yAS2Jc

Footnotes

  • This study was registered at Clinicaltrials.gov as NCT03080012.

  • Conflict of interest: S.H.J. van den Elsen has nothing to disclose.

  • Conflict of interest: O.W. Akkerman has nothing to disclose.

  • Conflict of interest: M. Wessels has nothing to disclose.

  • Conflict of interest: E.M. Jongedijk has nothing to disclose.

  • Conflict of interest: S. Ghimire has nothing to disclose.

  • Conflict of interest: T.S. van der Werf has nothing to disclose.

  • Conflict of interest: M.S. Bolhuis has nothing to disclose.

  • Conflict of interest: D.J. Touw has nothing to disclose.

  • Conflict of interest: J-W.C. Alffenaar has nothing to disclose.

  • Received March 22, 2020.
  • Accepted May 5, 2020.
  • Copyright ©ERS 2020
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Vol 56 Issue 4 Table of Contents
European Respiratory Journal: 56 (4)
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Dose optimisation of first-line tuberculosis drugs using therapeutic drug monitoring in saliva: feasible for rifampicin, not for isoniazid
Simone H.J. van den Elsen, Onno W. Akkerman, Mireille Wessels, Erwin M. Jongedijk, Samiksha Ghimire, Tjip S. van der Werf, Mathieu S. Bolhuis, Daan J. Touw, Jan-Willem C. Alffenaar
European Respiratory Journal Oct 2020, 56 (4) 2000803; DOI: 10.1183/13993003.00803-2020

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Dose optimisation of first-line tuberculosis drugs using therapeutic drug monitoring in saliva: feasible for rifampicin, not for isoniazid
Simone H.J. van den Elsen, Onno W. Akkerman, Mireille Wessels, Erwin M. Jongedijk, Samiksha Ghimire, Tjip S. van der Werf, Mathieu S. Bolhuis, Daan J. Touw, Jan-Willem C. Alffenaar
European Respiratory Journal Oct 2020, 56 (4) 2000803; DOI: 10.1183/13993003.00803-2020
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