8-Aminoquinolines: Primaquine and tafenoquine

Abstract

8-Aminoquinolines are an important class of antimalarial drugs because they are effective against the liver stages of Plasmodium infections and thus are administered for radical cure and presumptive antirelapse therapy against relapsing malaria. In this chapter, we discuss two 8-aminoquinolines, primaquine and tafenoquine. Primaquine was identified in 1946 and has been used extensively to clear liver-stage parasites, especially those from Plasmodium vivax. These can persist in the liver for months, as a dormant form of the parasite (the hypnozoite), which re-emerges much later to cause clinical disease. Tafenoquine, a primaquine analog, is currently under advanced clinical development. Tafenoquine has a much longer elimination half-life compared with primaquine (14 days versus 6 h) and is highly effective both in treating relapses of P. vivax malaria and as a causal prophylactic agent against P. falciparum and P. vivax malaria. A major drawback to the 8-aminoquinolines is their toxicity in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. We discuss clinical uses, pharmacokinetics and metabolism, safety and tolerability, mechanisms of action and drug resistance for both these drugs.