Pregnant women are particularly vulnerable to
malaria. The pharmacokinetic properties of
antimalarial drugs are often affected by pregnancy, resulting in lower drug concentrations and a consequently higher risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of
piperaquine and
dihydroartemisinin in pregnant and nonpregnant women with uncomplicated
malaria. Twenty-four pregnant and 24 matched nonpregnant women on the Thai-Myanmar boarder were treated with a standard fixed oral 3-day treatment, and venous plasma concentrations of both drugs were measured frequently for pharmacokinetic evaluation. Population pharmacokinetics were evaluated with nonlinear mixed-effects modeling. The main pharmacokinetic finding was an unaltered total exposure to
piperaquine but reduced exposure to
dihydroartemisinin in pregnant compared to nonpregnant women with uncomplicated
malaria.
Piperaquine was best described by a three-compartment disposition model with a 45% higher elimination clearance and a 47% increase in relative bioavailability in pregnant women compared with nonpregnant women. The resulting net effect of pregnancy was an unaltered total exposure to
piperaquine but a shorter terminal elimination half-life.
Dihydroartemisinin was best described by a one-compartment disposition model with a 38% lower relative bioavailability in pregnant women than nonpregnant women. The resulting net effect of pregnancy was a decreased total exposure to
dihydroartemisinin. The shorter terminal elimination half-life of
piperaquine and lower exposure to
dihydroartemisinin will shorten the posttreatment prophylactic effect and might affect cure rates. The clinical impact of these pharmacokinetic findings in pregnant women with uncomplicated
malaria needs to be evaluated in larger series.