Population Pharmacokinetics of Piperaquine after Two Different Treatment Regimens with Dihydroartemisinin-Piperaquine in Patients with Plasmodium falciparum Malaria in Thailand

<jats:title>ABSTRACT</jats:title> <jats:p>The population pharmacokinetics of piperaquine in adults and children with uncomplicated <jats:italic>Plasmodium falciparum</jats:italic> malaria treated with two different dosage regimens of dihydroartemisinin-piperaquine were characterized. Piperaquine pharmacokinetics in 98 Burmese and Karen patients aged 3 to 55 years were described by a two-compartment disposition model with first-order absorption and interindividual random variability on all parameters and were similar with the three- and four-dose regimens. Children had a lower body weight-normalized oral clearance than adults, resulting in longer terminal elimination half-lives and higher total exposure to piperaquine (area under the concentration-time curve from 0 to 63 days [AUC<jats:sub>day 0-63</jats:sub>]). However, children had lower plasma concentrations in the therapeutically relevant posttreatment prophylactic period (AUC<jats:sub>day 3-20</jats:sub>) because of smaller body weight-normalized central volumes of distribution and shorter distribution half-lives. Our data lend further support to a simplified once-daily treatment regimen to improve treatment adherence and efficacy and indicate that weight-adjusted piperaquine doses in children may need to be higher than in adults.</jats:p>