Tawanda Gumbo1, Jotam G Pasipanodya2, Eric Nuermberger3, Klaus Romero4, Debra Hanna4. 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.
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.
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Authors: Sander P van Rijn; Shashikant Srivastava; Mireille A Wessels; Dick van Soolingen; Jan-Willem C Alffenaar; Tawanda Gumbo Journal: Antimicrob Agents Chemother Date: 2017-08-24 Impact factor: 5.191
Authors: Devyani Deshpande; Jan-Willem C Alffenaar; Claudio U Köser; Keertan Dheda; Moti L Chapagain; Noviana Simbar; Thomas Schön; Marieke G G Sturkenboom; Helen McIlleron; Pooi S Lee; Thearith Koeuth; Stellah G Mpagama; Sayera Banu; Suporn Foongladda; Oleg Ogarkov; Suporn Pholwat; Eric R Houpt; Scott K Heysell; Tawanda Gumbo Journal: Clin Infect Dis Date: 2018-11-28 Impact factor: 9.079
Authors: Devyani Deshpande; Jotam G Pasipanodya; Stellah G Mpagama; Paula Bendet; Shashikant Srivastava; Thearith Koeuth; Pooi S Lee; Sujata M Bhavnani; Paul G Ambrose; Guy Thwaites; Scott K Heysell; Tawanda Gumbo Journal: Clin Infect Dis Date: 2018-11-28 Impact factor: 9.079
Authors: Beatriz E Ferro; Shashikant Srivastava; Devyani Deshpande; Jotam G Pasipanodya; Dick van Soolingen; Johan W Mouton; Jakko van Ingen; Tawanda Gumbo Journal: Antimicrob Agents Chemother Date: 2016-05-23 Impact factor: 5.191