Correlations Between the Hollow Fiber Model of Tuberculosis and Therapeutic Events in Tuberculosis Patients: Learn and Confirm. (28th July 2015)

• Record Type: Journal Article
• Authors: Gumbo, Tawanda; Pasipanodya, Jotam G.; Nuermberger, Eric; Romero, Klaus; Hanna, Debra
• Is Part Of: Clinical infectious diseases. Volume 61:(2015)Supplement 1
• Page Start: S18
• Page End: S24
• Publication Date: 2015-07-28
• Subjects: clinical correlations -- pharmacokinetics/pharmacodynamics -- dose-ranging -- dose-scheduling -- resistance emergence; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/civ426
• Languages: English
• ISSNs: 1058-4838

Abstract

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.