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Population Pharmacokinetics of Piperaquine after Two Different Treatment Regimens with Dihydroartemisinin-Piperaquine in Patients with Plasmodium falciparum Malaria in Thailand | Journal Article / Research | MSF Science Portal
Journal Article
|Research

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

Tarning J, Ashley EA, Lindegardh N, Stepniewska K, Phaiphun L, Day NPJ, McGready R, Ashton M, Nosten F, White NJ
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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.

Countries

Thailand

Subject Area

malariavector borne diseases

Languages

English
DOI
10.1128/AAC.00955-07
Published Date
01 Mar 2008
PubMed ID
18180343
Journal
Antimicrobial Agents and Chemotherapy
Volume | Issue | Pages
Volume 52, Issue 3
Issue Date
2008-03-01
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