title: Population pharmacokinetics of piperaquine after two different treatment regimens with dihydroartemisinin-piperaquine in patients with Plasmodium falciparum malaria in Thailand.
abstract: The population pharmacokinetics of piperaquine in adults and children with uncomplicated Plasmodium falciparum 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 day 0-63]). However, children had lower plasma concentrations in the therapeutically relevant posttreatment prophylactic period (AUC day 3-20) 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.
authors.affiliation: Department of Pharmacology, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Tarning
authors.forename: E A
authors.initials: EA
authors.lastname: Ashley
authors.forename: N
authors.initials: N
authors.lastname: Lindegardh
authors.forename: K
authors.initials: K
authors.lastname: Stepniewska
authors.forename: L
authors.initials: L
authors.lastname: Phaiphun
authors.forename: N P J
authors.initials: NP
authors.lastname: Day
authors.forename: R
authors.initials: R
authors.lastname: McGready
authors.forename: M
authors.initials: M
authors.lastname: Ashton
authors.forename: F
authors.initials: F
authors.lastname: Nosten
authors.forename: N J
authors.initials: NJ
authors.lastname: White
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013785:Thailand; D016896:Treatment Outcome; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines