title: Current status and opportunities for therapeutic drug monitoring in the treatment of tuberculosis.
abstract: BACKGROUND
  Tuberculosis remains a global health problem and pharmacokinetic variability has been postulated as one of the causes of treatment failure and acquired drug resistance. New developments enable implementation of therapeutic drug monitoring, a strategy to evaluate drug exposure in order to tailor the dose to the individual patient, in tuberculosis treatment.
  
  
  METHODS
  Literature on pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs was explored to evaluate the effect of drug exposure in relation to drug susceptibility, toxicity and efficacy. New, down-sized strategies, like dried blood spot analysis and limited sampling strategies are reviewed. In addition, molecular resistance testing of Mycobacteria tuberculosis, combining a short turn-around time with relevant information on drug susceptibility of the causative pathogen was explored. Newly emerging host biomarkers provide information on the response to treatment.
  
  
  CONCLUSIONS
  Therapeutic drug monitoring can minimize toxicity and increase efficacy of tuberculosis treatment and prevent the development of resistance. Dried blood spot analysis and limited sampling strategies, can be combined to provide us with a more patient friendly approach. Furthermore, rapid information on drug susceptibility by molecular testing, and information from host biomarkers on the bacteriological response, can be used to further optimize tuberculosis treatment.
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology , University of Groningen, University Medical Center Groningen , Groningen , The Netherlands.
authors.forename: Marlanka A
authors.initials: MA
authors.lastname: Zuur
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology , University of Groningen, University Medical Center Groningen , Groningen , The Netherlands.
authors.forename: Mathieu S
authors.initials: MS
authors.lastname: Bolhuis
authors.affiliation: b Royal Tropical Institute (KIT) , KIT Biomedical Research , Amsterdam , The Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: Anthony
authors.affiliation: b Royal Tropical Institute (KIT) , KIT Biomedical Research , Amsterdam , The Netherlands.
authors.forename: Alice
authors.initials: A
authors.lastname: den Hertog
authors.affiliation: c National Tuberculosis Reference Laboratory , National Institute for Public Health and the Environment (RIVM) , Bilthoven , The Netherlands.
authors.forename: Tridia
authors.initials: T
authors.lastname: van der Laan
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology , University of Groningen, University Medical Center Groningen , Groningen , The Netherlands.|d Department of Pharmacy, section Pharmacotherapy and Pharmaceutical Care , University of Groningen , Groningen , The Netherlands.
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
authors.affiliation: e University of Groningen, University Medical Center Groningen , Tuberculosis Centre Beatrixoord , Haren , The Netherlands.|f Department of Pulmonary Diseases and Tuberculosis , University of Groningen, University Medical Center Groningen , Groningen , The Netherlands.
authors.forename: Wiel
authors.initials: W
authors.lastname: de Lange
authors.affiliation: c National Tuberculosis Reference Laboratory , National Institute for Public Health and the Environment (RIVM) , Bilthoven , The Netherlands.|g Departments of Pulmonary Diseases and Medical Microbiology , Radboud University Nijmegen Medical Center , Nijmegen , The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: van Soolingen
authors.affiliation: a Department of Clinical Pharmacy and Pharmacology , University of Groningen, University Medical Center Groningen , Groningen , The Netherlands.
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D059788:Dried Blood Spot Testing / Q000379:methods; D016903:Drug Monitoring / Q000379:methods*; D024881:Drug Resistance, Bacterial; D014943:Global Health; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents
keywords: Biomarkers; dried blood spots; drug susceptibility testing; limited sampling; molecular testing; pharmacokinetics/pharmacodynamics; therapeutic drug monitoring; tuberculosis treatment