A study of the plasma concentration-time profile and antimalarial activity of plasma samples collected from healthy Vietnamese volunteers after the administration of artesunate-amodiaquine alone and with methylene blue.

Artemisinin combination therapies (ACT) such as artesunate-amodiaquine (ASAQ) are currently recommended worldwide for first-line treatment of uncomplicated Plasmodium falciparum malaria. However, recent reports of reduced susceptibility of artemisinins and ACTs in western Cambodia, western Thailand and south Vietnam is very worrisome and highlights the urgent need to identify alternative drug combination options for effective and affordable treatment. To extend the efficacy life of ACTs, a triple drug combination strategy may be worthy of consideration. We propose to determine whether methylene blue (MB), an old and affordable antimalarial drug, can be combined with ASAQ to extend the efficacy life of the ACT by studying the tolerability, pharmacokinetics and ex vivo antimalarial activity of ASAQ alone and with MB in healthy Vietnamese volunteers. If MB combined with ASAQ is well tolerated and does not adversely alter the pharmacokinetics of ASAQ in healthy volunteers, and enhanced blood stage ex vivo antimalarial activity can be demonstrated in volunteers' plasma containing ASAQ plus MB, then further studies a warranted to appraise the clinical value of the triple drug combination of AS+AQ+MB.