Integrating Pharmacokinetics and Pharmacodynamics in Operational Research to End Tuberculosis

Abstract

Tuberculosis (TB) elimination requires innovative approaches. The new Global Tuberculosis Network (GTN) aims to conduct research on key unmet therapeutic and diagnostic needs in the field of TB elimination using multidisciplinary, multisectorial approaches. The TB Pharmacology section within the new GTN aims to detect and study the current knowledge gaps, test potential solutions using human pharmacokinetics informed through preclinical infection systems, and return those findings to the bedside. Moreover, this approach would allow prospective identification and validation of optimal shorter therapeutic durations with new regimens. Optimized treatment using available and repurposed drugs may have an increased impact when prioritizing a person-centered approach and acknowledge the importance of age, gender, comorbidities, and both social and programmatic environments. In this viewpoint article, we present an in-depth discussion on how TB pharmacology and the related strategies will contribute to TB elimination.

Keywords: drug resistance; pharmacodynamics; pharmacokinetics; therapeutic drug monitoring; tuberculosis.

Figure 1.

Individualized management of tuberculosis using operational PK/PD research. In general, PK/PD research is patient-centered and uses information on the susceptibility of the pathogen being either phenotypic or genotypic, subsequently using a measure of drug exposure and correlate both in relation to treatment outcome or any other measure of treatment response in a real-life setting. Abbreviations: gDST, genotypic drug susceptibility testing; pDST, phenotypic drug susceptibility testing; PK, pharmacokinetic; TB, tuberculosis; TDM, therapeutic drug monitoring. * key drugs for TDM include rifampicin, pyrazinamide, isoniazid, levofloxacin, moxifloxacin, and linezolid.