The Importance of Clinical Pharmacokinetic-pharmacodynamic Studies in Unraveling the Determinants of Early and Late Tuberculosis Outcomes

Overview

Journal Int J Pharmacokinet

Date 2018 Oct 5

PMID 30283633

Citations 10

Authors

Andrew D McCallum

Derek J Sloan

Affiliations

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Abstract

Tuberculosis remains a major infectious cause of morbidity and mortality worldwide. Current antibiotic regimens, constructed prior to the development of modern pharmacokinetic-pharmacodynamic (PK-PD) tools, are based on incomplete understanding of exposure-response relationships in drug susceptible and multidrug resistant tuberculosis. Preclinical and population PK data suggest that clinical PK-PD studies may enable therapeutic drug monitoring for some agents and revised dosing for others. Future clinical PK-PD challenges include: incorporation of PK methods to assay free concentrations for all active metabolites; selection of appropriate early outcome measures which reflect therapeutic response; elucidation of genetic contributors to interindividual PK variability; conduct of targeted studies on special populations (including children); and measurement of PK-PD parameters at the site of disease.

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