Chapter 10

Efforts to Improve Antimalarial Combination Therapy

Qigui Li and Mark R. Hickman

Abstract

Several drug development strategies for novel antimalarial drugs have been created to counter the rise of malaria drug resistance. These strategies include optimizing new antimalarial drug combinations through laboratory testing and clinical development. ACTs are the most successful drug combinations invented to date for treatment of malaria worldwide, however, the growing tide of malaria resistance, particularly in Southeast Asia, provides a compelling need to discover novel chemical entities to combine with artemisinin analogues or create new antimalarial combinations using existing drugs. Strategies to find novel chemical entities are outlined in this section ranging from irrational drug discovery with whole-cell phenotypic screening to target based screening against specific Plasmodium targets. Implementation of antimalarial drug combinations with diverse PK/PD profiles will likely require evaluation of multiple outcomes, which further complicates statistical modelling for factorial designs. Well- constructed, carefully conducted, and statistically rigorous clinical pharmacology studies are necessary for development of new malaria treatments and practical methods must be put in place for post licensure marketing surveillance to detect both emerging drug resistance and adverse effects. While a number of novel chemical entities are under development, bringing new, efficacious, safe, and welltolerated antimalarial drugs to market is a quite a challenge particularly in today’s regulatory environment. In addition, antimalarial treatment currently involves combinations of drugs with synergistic or additive properties, which makes drug discovery and development even more challenging.

Total Pages: 441-482 (42)

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