Format

Send to

Choose Destination
Clin Infect Dis. 2015 Aug 15;61 Suppl 1:S18-24. doi: 10.1093/cid/civ426.

Correlations Between the Hollow Fiber Model of Tuberculosis and Therapeutic Events in Tuberculosis Patients: Learn and Confirm.

Author information

1
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.
2
Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
3
Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.
4
Critical Path to TB Drug Regimens, Critical Path Institute, Tucson, Arizona.

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.

KEYWORDS:

clinical correlations; dose-ranging; dose-scheduling; pharmacokinetics/pharmacodynamics; resistance emergence

PMID:
26224768
DOI:
10.1093/cid/civ426
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center