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Antimicrobial Agents and Chemotherapy, March 2008, p. 1052-1061, Vol. 52, No. 3
0066-4804/08/$08.00+0     doi:10.1128/AAC.00955-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

J. Tarning,1,3 E. A. Ashley,2,3,4,5 N. Lindegardh,3,4 K. Stepniewska,3,4 L. Phaiphun,2 N. P. J. Day,3,4 R. McGready,2,3,4 M. Ashton,1 F. Nosten,2,3,4 and N. J. White3,4*

Department of Pharmacology, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden,1 Shoklo Malaria Research Unit, Mae Sot, Thailand,2 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand,3 Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom,4 Epicentre, 8 rue Saint Sabin, 75011 Paris, France5

Received 25 July 2007/ Returned for modification 30 October 2007/ Accepted 28 December 2007

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 [AUCday 0-63]). However, children had lower plasma concentrations in the therapeutically relevant posttreatment prophylactic period (AUCday 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.

* Corresponding author. Mailing address: Mahidol - Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. Phone: 662 354 9172. Fax: 662 354 9169. E-mail: nickw{at}tropmedres.ac

{triangledown} Published ahead of print on 7 January 2008.

Antimicrobial Agents and Chemotherapy, March 2008, p. 1052-1061, Vol. 52, No. 3
0066-4804/08/$08.00+0     doi:10.1128/AAC.00955-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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