The tolerability, safety and disposition of dihydroartemisinin (DHA) and piperaquine (PQ) were assessed in 32 pregnant (second/third trimester) and 33 non-pregnant Papua New Guinean women randomized to adult treatment courses of DHA-PQ (three daily doses) or sulfadoxine-pyrimethamine-PQ (three daily PQ doses, single-dose SP). All doses were observed and subjects fasted for 2 h post-dose. Plasma PQ was assayed by high performance liquid chromatography and DHA by liquid chromatography-mass spectrometry. Compartmental pharmacokinetic models were developed using a population-based approach. Both regimens were well tolerated. There was an expected increase in rate-corrected electrocardiographic QT interval which was independent of pregnancy and treatment. Two pregnant and two non-pregnant women had Plasmodium falciparum parasitaemia. Parasite clearance was <48 h and no other subject became slide positive for malaria during 42 days of follow-up. Of 30 pregnant women followed to delivery, 27 (90%) delivered healthy babies and 3 (10%) had stillbirths, obstetric outcomes consistent with those in the general population.

 

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