Current status of pharmacokinetic and safety studies of multidrug-resistant tuberculosis treatment in children

A. J. Garcia-Prats, E. M. Svensson, Ethel Weld, H. S. Schaaf, A. C. Hesseling

Research output: Contribution to journalArticle

Abstract

After decades of neglect, data are finally becoming available on the appropriate, safe dosing of key second-line anti-tuberculosis drugs used for treating multidrug-resistant tuberculosis (MDR-TB) in children, including levofloxacin (LVX), moxifloxacin (MFX), linezolid (LZD) and delamanid (DLM). Much needed data on some novel and repurposed drugs are still lacking, including for bedaquiline (BDQ), pretomanid (PTM) and clofazimine (CFZ). We review the status of pharmacokinetic (PK) and safety studies of key anti-tuberculosis medications in children with MDR-TB, identify priority knowledge gaps and note ongoing work to address those gaps, in the context of planning for an efficacy trial in children with MDR-TB. There is international consensus that an efficacy trial of a novel, all-oral, shortened MDR-TB treatment trial in children is both needed and feasible. Key novel and repurposed second-line anti-tuberculosis drugs include BDQ, DLM, PTM, MFX, LVX, CFZ and LZD. The rapidly emerging PK and safety data on these medications in children with MDR-TB from studies that are underway, completed or planned, will be critical in supporting such an efficacy trial. Commitment to addressing the remaining knowledge gaps, developing child-friendly formulations of key medications, improving the design of paediatric PK and safety studies, and development of international trial capacity in children with MDR-TB are important priorities.

Original languageEnglish (US)
Pages (from-to)15-23
Number of pages9
JournalThe international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Volume22
Issue number5
DOIs
StatePublished - May 1 2018

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Multidrug-Resistant Tuberculosis
Pharmacokinetics
Linezolid
Safety
bedaquiline
Clofazimine
Levofloxacin
Tuberculosis
Therapeutics
Drug Repositioning
Pharmaceutical Preparations
Pediatrics

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

Cite this

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