title: Correlations Between the Hollow Fiber Model of Tuberculosis and Therapeutic Events in Tuberculosis Patients: Learn and Confirm.
abstract: BACKGROUND
  The hollow fiber system model of tuberculosis (HFS-TB) is designed to perform pharmacokinetics/pharmacodynamics (PK/PD) experiments, and hence the design of optimal doses and dose schedules for the treatment of tuberculosis. To determine if this model is useful for deriving PK/PD data relevant to clinical outcomes, we compared its quantitative output to that from clinical trials.
  
  
  METHODS
  We performed a PubMed search to identify clinical studies performed with antituberculosis therapy in which PK/PD data and/or parameters were documented or a dose-scheduling study design was employed. The search period was from January 1943 to December 2012. All clinical studies were published prior to HFS-TB experiments. Bias minimization was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Clinical publications were scored for quality of evidence, with 1 as the highest score (randomized controlled trials or meta-analyses of such studies), and 4 as the lowest score.
  
  
  RESULTS
  We identified 17 studies that examined the same parameters as in 8 HFS-TB studies. Fifteen of 17 studies had a quality-of-evidence score of 1. The sterilizing and bactericidal effect rates for isoniazid, rifampin, pyrazinamide, and ethambutol were the same in the HFS-TB as in patients. Time to emergence of resistance for monotherapy was the same as in patients. The PK/PD indices associated with efficacy were the same in HFS-TB as in patients for all drugs examined.
  
  
  CONCLUSIONS
  The HFS-TB model is highly accurate at identifying optimal drug exposures, doses, and dosing schedules for use in the clinic.
authors.affiliation: Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas Department of Medicine, University of Cape Town, Observatory, South Africa.
authors.forename: Tawanda
authors.initials: T
authors.lastname: Gumbo
authors.affiliation: Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
authors.forename: Jotam G
authors.initials: JG
authors.lastname: Pasipanodya
authors.affiliation: Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Eric
authors.initials: E
authors.lastname: Nuermberger
authors.affiliation: Critical Path to TB Drug Regimens, Critical Path Institute, Tucson, Arizona.
authors.forename: Klaus
authors.initials: K
authors.lastname: Romero
authors.affiliation: Critical Path to TB Drug Regimens, Critical Path Institute, Tucson, Arizona.
authors.forename: Debra
authors.initials: D
authors.lastname: Hanna
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D024881:Drug Resistance, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin
keywords: clinical correlations; dose-ranging; dose-scheduling; pharmacokinetics/pharmacodynamics; resistance emergence