The implications of model-informed drug discovery and development for tuberculosis.
Despite promising advances in the field and highly efficacious first-line treatment, an estimated 9.6 million people are still infected with tuberculosis (TB). Innovative methods are required to effectively transition the growing number of compounds into novel combination regimens. However, progression of compounds into patients occurs despite the lack of clear understanding of the pharmacokinetic-pharmacodynamic (PKPD) relationships. The PreDiCT-TB consortium was established in response to the existing gaps in TB drug development. The aim of the consortium is to develop new preclinical tools in concert with an in silico model-based approach, grounded in PKPD principles. Here, we highlight the potential impact of such an integrated framework on the various stages of TB drug development and on the dose rationale for drug combinations.
UCL School of Life and Medical Sciences, London, UK.
Morris
M
Muliaditan
Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Geraint R
GR
Davies
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Ulrika S H
USH
Simonsson
School of Medicine, University of St Andrews, St Andrews, UK.
Stephen H
SH
Gillespie
UCL School of Life and Medical Sciences, London, UK; GlaxoSmithKline, London, UK. Electronic address: o.dellapasqua@ucl.ac.uk.
Oscar
O
Della Pasqua
D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use; D017277:Drug Approval; D055808:Drug Discovery; D006801:Humans; D008962:Models, Theoretical; D014376:Tuberculosis / Q000188:drug therapy
D000995:Antitubercular Agents