In vitro pharmacokinetic/pharmacodynamic models in anti-infective drug development

Focus on TB

Pavan K. Vaddady, Richard E. Lee, Bernd Meibohm

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

For rapid anti-tuberculosis (TB) drug development in vitro pharmacokinetic/pharmacodynamic (PK/PD) models are useful in evaluating the direct interaction between the drug and the bacteria, thereby guiding the selection of candidate compounds and the optimization of their dosing regimens. Utilizing in vivo drug-clearance profiles from animal and/or human studies and simulating them in an in vitro PK/PD model allows the in-depth characterization of antibiotic activity of new and existing antibacterials by generating time-kill data. These data capture the dynamic interplay between mycobacterial growth and changing drug concentration as encountered during prolonged drug therapy. This review focuses on important PK/PD parameters relevant to anti-TB drug development, provides an overview of in vitro PK/PD models used to evaluate the efficacy of agents against mycobacteria and discusses the related mathematical modeling approaches of time-kill data. Overall, it provides an introduction to in vitro PK/PD models and their application as critical tools in evaluating anti-TB drugs.

Original languageEnglish (US)
Pages (from-to)1355-1369
Number of pages15
JournalFuture Medicinal Chemistry
Volume2
Issue number8
DOIs
StatePublished - Aug 1 2010

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Tuberculosis
Pharmacokinetics
Pharmaceutical Preparations
Mycobacterium
Drug Interactions
In Vitro Techniques
Anti-Bacterial Agents
Bacteria
Drug Therapy
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

In vitro pharmacokinetic/pharmacodynamic models in anti-infective drug development : Focus on TB. / Vaddady, Pavan K.; Lee, Richard E.; Meibohm, Bernd.

In: Future Medicinal Chemistry, Vol. 2, No. 8, 01.08.2010, p. 1355-1369.

Research output: Contribution to journalReview article

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