Interactions between tafenoquine and artemisinin-combination therapy partner drug in asexual and sexual stage Plasmodium falciparum

- Interactions of tafenoquine with other antimalarials are studied in P. falciparum.
- Synergistic interactions occur with most drugs in asexual erythrocytic stages.
- Tafenoquine will likely increase the potency of other drugs against asexual stages.
- Synergism is found with naphthoquine, pyronaridine and piperaquine in gametocytes.
- Tafenoquine may interfere with other drugs against P. falciparum gametocytes.

The 8-aminoquinoline tafenoquine (TFQ), a primaquine derivative, is currently in late-stage clinical development for the radical cure of P. vivax. Here drug interactions between TFQ and chloroquine and six artemisinin-combination therapy (ACT) partner drugs in P. falciparum asexual stages and gametocytes were investigated. TFQ was mostly synergistic with the ACT-partner drugs in asexual parasites regardless of genetic backgrounds. However, at fixed ratios of 1:3, 1:1 and 3:1, TFQ only interacted synergistically with naphthoquine, pyronaridine and piperaquine in gametocytes. This study indicated that TFQ and ACT-partner drugs will likely have increased potency against asexual stages of the malaria parasites, whereas some drugs may interfere with each other against the P. falciparum gametocytes.

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