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Antimicrobial Agents and Chemotherapy, January 2008, p. 237-243, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.00555-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics and Efficacy of Piperaquine and Chloroquine in Melanesian Children with Uncomplicated Malaria{triangledown}

Harin A. Karunajeewa,1 Kenneth F. Ilett,1 Ivo Mueller,2 Peter Siba,2 Irwin Law,1 Madhu Page-Sharp,1 Enmoore Lin,2 Jovitha Lammey,2 Kevin T. Batty,3 and Timothy M. E. Davis1*

School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia,1 Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea,2 School of Pharmacy, Curtin University, Bentley, Western Australia, Australia3

Received 26 April 2007/ Returned for modification 2 July 2007/ Accepted 17 October 2007

The disposition of chloroquine (CQ) and the related 4-aminoquinoline, piperaquine (PQ), were compared in Papua New Guinean children with uncomplicated malaria. Twenty-two children were randomized to 3 days of PQ phosphate at 20 mg/kg/day (12 mg of PQ base/kg/day) coformulated with dihydroartemisinin (DHA-PQ), and twenty children were randomized to 3 days of CQ at 10 mg base/kg/day with a single dose of sulfadoxine-pyrimethamine (CQ-SP). After a 42-day intensive sampling protocol, PQ, CQ, and its active metabolite monodesethyl-chloroquine (DECQ) were assayed in plasma by using high-performance liquid chromatography. A two-compartment model with first-order absorption was fitted to the PQ and CQ data. There were no significant differences in age, gender, body weight, or admission parasitemia between the two groups. The PCR-corrected 42-day adequate clinical and parasitological responses were 100% for DHA-PQ and 94% for CQ-SP, but P. falciparum reinfections during follow-up were common (33 and 18%, respectively). For PQ, the median volume of distribution at steady state, allowing for bioavailability (Vss/F), was 431 liters/kg (interquartile range [IQR], 283 to 588 liters/kg), the median clearance (CL/F) was 0.85 liters/h/kg (IQR, 0.67 to 1.06 liters/h/kg), the median distribution half-life (t1/2{alpha}) was 0.12 h (IQR, 0.05 to 0.66 h), and the median elimination half-life (t1/2β) was 413 h (IQR, 318 to 516 h). For CQ, the median Vss/F was 154 liters/kg (IQR, 101 to 210 liters/kg), the median CL/F was 0.80 liters/h/kg (IQR, 0.52 to 0.96 liters/h/kg), the median t1/2{alpha} was 0.43 h (IQR, 0.05 to 1.82 h), and the median t1/2β was 233 h (IQR, 206 to 298 h). The noncompartmentally derived median DECQ t1/2β was 290 h (IQR, 236 to 368 h). Combined molar concentrations of DECQ and CQ were higher than those of PQ during the elimination phase. Although PQ has a longer t1/2β than CQ, its prompt distribution and lack of active metabolite may limit its posttreatment malaria-suppressive properties.

* Corresponding author. Mailing address: Department of Medicine, Fremantle Hospital, P.O. Box 480, Fremantle 6959, Western Australia, Australia. Phone: (618) 9431-3229. Fax: (618) 9431-2977. E-mail: tdavis{at}cyllene.uwa.edu.au

{triangledown} Published ahead of print on 29 October 2007.

Antimicrobial Agents and Chemotherapy, January 2008, p. 237-243, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.00555-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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