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Antimicrobial Agents and Chemotherapy, June 2005, p. 2407-2411, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2407-2411.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Effects of a High-Fat Meal on the Relative Oral Bioavailability of Piperaquine

Ing-Kye Sim,1 Timothy M. E. Davis,1 and Kenneth F. Ilett1,2*

Medicine Unit Fremantle and Pharmacology Unit Nedlands, School of Medicine and Pharmacology, University of Western Australia, Crawley,1 Clinical Pharmacology and Toxicology Laboratory, The Western Australian Centre for Pathology and Medical Research, Nedlands, Australia2

Received 22 November 2004/ Returned for modification 19 January 2005/ Accepted 27 February 2005

Piperaquine (PQ) is an antimalarial drug whose high lipid solubility suggests that its absorption can be increased by a high-fat meal. We examined the pharmacokinetics of PQ phosphate (500 mg given orally) in the fasting state and after a high-fat meal in eight healthy Caucasian volunteers (randomized crossover). Plasma PQ concentration-time profiles were analyzed by using noncompartmental pharmacokinetic analysis. In the fed state, the geometric mean Cmax increased by 213%, from 21.0 to 65.8 µg/liter (P < 0.001). The time of Cmax was not significantly different between the fasting and fed states. The geometric mean area under the concentration-time curve from zero onward (AUC0-{infty}) increased by 98%, from 3,724 to 7,362 µg h/liter (P = 0.006). The oral bioavailability of PQ relative to the fasting state was 121% greater after the high-fat meal (95% confidence interval, 26 to 216% increase; P = 0.020). The side effects, postural blood pressure changes, electrocardiographic corrected QT interval, serum glucose, and other biochemical and hematological indices were similar in the fasting and fed states over 28 days of follow-up.

* Corresponding author. Mailing address: Pharmacology Unit, M510, School of Medicine and Pharmacology, University of Western Australia, Crawley 6009, Australia. Phone: 618-9346-2985. Fax: 618-9346-3649. E-mail: kilett{at}receptor.pharm.uwa.edu.au.

Antimicrobial Agents and Chemotherapy, June 2005, p. 2407-2411, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2407-2411.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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