Dihydroartemisinin-
piperaquine is an effective
drug in the treatment of Plasmodium falciparum and P.
vivax malaria. The objective of this study was to evaluate the population pharmacokinetics and pharmacodynamics of
piperaquine in patients with P.
vivax malaria in Thailand after a standard regimen of
dihydroartemisinin-
piperaquine to determine whether residual
piperaquine prevents or delays the emergence of P. vivax relapse. Sparse blood samples were collected from 116 patients.
Piperaquine pharmacokinetics were described well by a three-compartment distribution model. Relapsing P.
vivax malaria was accommodated by a constant baseline hazard (8.94 relapses/year) with the addition of a surge function in a fixed 3-week interval and a protective
piperaquine effect. The results suggest that a large proportion of the first relapses were suppressed completely by residual
piperaquine concentrations and that recurrences resulted mainly from emergence of the second or third relapse or from
reinfection. This suggests a significant reduction in P. vivax morbidity when using
dihydroartemisinin-
piperaquine compared with other
antimalarial drugs with shorter terminal postprophylactic effects.