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Quantitative Assessment of the Activity of Antituberculosis Drugs and Regimens

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Date 2019 May 31
PMID 31144539
Citations 1
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Abstract

: Identification of optimal drug doses and drug combinations is crucial for optimized treatment of tuberculosis. : An unprecedented level of research activity involving multiple approaches is seeking to improve tuberculosis treatment. This report is a review of the quantitative methods currently used on clinical data sets to identify drug exposure targets and optimal drug combinations for tuberculosis treatment. A high-level summary of the methods, including the strengths and weaknesses of each method and potential methodological improvements is presented. Methods incorporating data generated from multiple sources such as and clinical studies, and their potential to provide better estimates of pharmacokinetic/pharmacodynamic (PK/PD) targets, are discussed. PK/PD relationships identified are compared between different studies and data analysis methods. : The relationships between drug exposures and tuberculosis treatment outcomes are complex and require analytical methods capable of handling the multidimensional nature of the relationships. The choice of a method is guided by its complexity, interpretability of results, and type of data available.

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References
1.
Deshpande D, Pasipanodya J, Mpagama S, Srivastava S, Bendet P, Koeuth T . Ethionamide Pharmacokinetics/Pharmacodynamics-derived Dose, the Role of MICs in Clinical Outcome, and the Resistance Arrow of Time in Multidrug-resistant Tuberculosis. Clin Infect Dis. 2018; 67(suppl_3):S317-S326. PMC: 6260165. DOI: 10.1093/cid/ciy609. View

2.
Chideya S, Winston C, Peloquin C, Bradford W, Hopewell P, Wells C . Isoniazid, rifampin, ethambutol, and pyrazinamide pharmacokinetics and treatment outcomes among a predominantly HIV-infected cohort of adults with tuberculosis from Botswana. Clin Infect Dis. 2009; 48(12):1685-94. PMC: 3762461. DOI: 10.1086/599040. View

3.
Gumbo T, Alffenaar J . Pharmacokinetic/Pharmacodynamic Background and Methods and Scientific Evidence Base for Dosing of Second-line Tuberculosis Drugs. Clin Infect Dis. 2018; 67(suppl_3):S267-S273. PMC: 6260166. DOI: 10.1093/cid/ciy608. View

4.
Lenaerts A, Barry 3rd C, Dartois V . Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses. Immunol Rev. 2015; 264(1):288-307. PMC: 4368385. DOI: 10.1111/imr.12252. View

5.
Guiastrennec B, Ramachandran G, Karlsson M, Hemanth Kumar A, Bhavani P, Poorana Gangadevi N . Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications. Clin Pharmacol Ther. 2017; 104(4):733-741. PMC: 6004234. DOI: 10.1002/cpt.987. View