title: Understanding pharmacokinetics to improve tuberculosis treatment outcome.
abstract: BACKGROUND
  Tuberculosis (TB) remains the leading cause of death from a curable infectious disease; drug-resistant TB threatens to dismantle all prior gains in global control. Suboptimal circulating anti-TB drug concentrations can lead to lack of cure and acquired drug resistance.
  
  
  METHODS
  This review will introduce pharmacokinetic parameters for key anti-TB drugs, as well as the indications and limitations of measuring these parameters in clinical practice. Current and novel methodologies for delivering anti-TB pharmacokinetic-pharmacodynamic data are highlighted and gaps in operational research described.
  
  
  CONCLUSIONS
  Individual pharmacokinetic variability is commonplace, underappreciated and difficult to predict without therapeutic drug monitoring (TDM). Pharmacokinetic thresholds associated with poor TB treatment outcome in drug-susceptible TB have recently been described and may now guide the application of TDM, but require validation in a variety of settings and comorbidities. Dried blood spots for TDM and prepackaged multidrug plates for minimum inhibitory concentration testing will overcome barriers of accessibility and represent areas for innovation. Operationalizing pharmacokinetics has the potential to improve TB outcomes in the most difficult-to-treat forms of the disease such as multidrug resistance. Clinical studies in these areas are eagerly anticipated and we expect will better define the rational introduction of novel therapeutics.
authors.affiliation: University of Virginia, School of Medicine , PO Box 801340, Charlottesville, VA 22908-1340 , USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Reynolds
authors.forename: Scott K
authors.initials: SK
authors.lastname: Heysell
mesh_terms: D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003920:Diabetes Mellitus; D016903:Drug Monitoring; D004977:Ethambutol / Q000493:pharmacokinetics / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007538:Isoniazid / Q000493:pharmacokinetics / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D011718:Pyrazinamide / Q000493:pharmacokinetics / Q000627:therapeutic use; D012294:Rifamycins / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D012294:Rifamycins; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid
keywords: dried blood spot; minimum inhibitory concentration; multidrug-resistant tuberculosis; pharmacokinetics; therapeutic drug monitoring; tuberculosis