Pharmacokinetics of Piperaquine in Pregnant Women in Sudan with Uncomplicated Plasmodium falciparum Malaria

The pharmacokinetic properties of piperaquine were investigated in 12 pregnant and 12 well-matched, nonpregnant women receiving a three-day oral fixed dose combination regimen of dihydroartemisinin and piperaquine for treatment of uncomplicated Plasmodium falciparum at New Haifa Hospital in eastern Sudan. Frequent venous plasma samples were drawn from the patients over a 63-day period and a complete concentration-time profile was collected for 7 pregnant and 11 non-pregnant patients. Piperaquine was quantified using a liquid chromatography-mass spectrometry/mass spectrometry method. Pregnant women had a significantly higher total drug exposure (median area under the curve [range] = 1,770 [1,200-5,600] hr x ng/mL versus 858 [325-2,370] hr x ng/mL; P = 0.018) and longer time to maximal concentration (4.00 [1.50-4.03] hr versus 1.50 [0.500-8.00] hr; P = 0.02) after the first dose compared with non-pregnant women. There was no other significant difference observed in piperaquine pharmacokinetics between pregnant and nonpregnant women, including no difference in total drug exposure or maximum concentration. The overall pharmacokinetic properties of piperaquine in this study were consistent with previously published reports in non-pregnant patients.