Exploiting knowledge on pharmacodynamics-pharmacokinetics for accelerated anti-leishmanial drug discovery/development

Expert Opin Drug Metab Toxicol. 2019 Jul;15(7):595-612. doi: 10.1080/17425255.2019.1629417. Epub 2019 Jun 17.

Abstract

Introduction: Being on the top list of neglected tropical diseases, leishmaniasis has been marked for elimination by 2020. In the light of small armamentarium of drugs and their associated drawbacks, the understanding of pharmacodynamics and/or pharmacokinetics becomes a priority to achieve and sustain disease elimination. Areas covered: The authors have looked into pharmacological aspects of existing and emerging drugs for treatment of leishmaniasis. An in-depth understanding of pharmacodynamics and pharmacokinetics (PKPD) provides a rationale for drug designing and optimizing the treatment strategies. It forms a key to prevent drug resistance and avoid drug-associated adverse effects. The authors have compiled the researches on the PKPD of different anti-leishmanial formulations that have the potential for improved and/or effective disease intervention. Expert opinion: Understanding the pharmacological aspects of drugs forms the basis for the clinical application of novel drugs. Tailoring drug dosage and individualized treatment can avoid the adverse events and bridge gap between the in vitro models and their clinical application. An integrated approach, with pragmatic use of technological advances can improve phenotypic screening and physiochemical properties of novel drugs. Concomitantly, this can serve to improve clinical efficacies, reduce the incidence of relapse and accelerate the drug discovery/development process for leishmaniasis elimination.

Keywords: Pharmacology; combination therapy; host directed therapy; nano-formulations.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiprotozoal Agents / administration & dosage*
  • Antiprotozoal Agents / pharmacokinetics
  • Antiprotozoal Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Design
  • Drug Development / methods*
  • Drug Discovery / methods
  • Drug Resistance
  • Humans
  • Leishmaniasis / drug therapy*
  • Leishmaniasis / parasitology

Substances

  • Antiprotozoal Agents