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Type: Journal article
Title: Effect of food on the pharmacokinetics of piperaquine and dihydroartemisinin
Author: Reuter, S.
Evans, A.
Shakib, S.
Lungershausen, Y.
Francis, B.
Valentini, G.
Bacchieri, A.
Ubben, D.
Pace, S.
Citation: Clinical Drug Investigation, 2015; 35(9):559-567
Publisher: Springer
Issue Date: 2015
ISSN: 1173-2563
Statement of
Stephanie E. Reuter, Allan M. Evans, Sepehr Shakib, Yvonne Lungershausen, Barbara Francis, Giovanni Valentini, Antonella Bacchieri, David Ubben, Silvia Pace
Abstract: BACKGROUND AND OBJECTIVE Piperaquine–dihydroartemisinin combination therapy has established efficacy for the treatment of malaria; however, a more comprehensive understanding of the pharmacokinetic properties and factors contributing to inter- and intra-individual variability is critical to optimize clinical use. This study assessed the effects of food on the pharmacokinetics of combination piperaquine–dihydroartemisinin administration in healthy volunteers. METHODS This was an open-label, single-dose, parallel-group study. Participants were randomly allocated to receive oral piperaquine–dihydroartemisinin either after an overnight fast or immediately after a standardized, high-fat, high-calorie meal. Blood samples were collected for analysis of plasma piperaquine and dihydroartemisinin concentrations, which were utilized for calculation of pharmacokinetic parameters, using a standard model-independent approach. RESULTS Consumption of a high-fat, high-calorie meal resulted in substantial increases in the extent of exposure to piperaquine (ratio between area under the plasma concentration–time curve [AUC] values from 0 to 168 h in the fed and fasted states [AUC0–168 h FED/AUC0–168 h FASTED] = 299 %, 90 % confidence interval [CI] 239–374 %). This likely reflects an increase in the oral bioavailability of the drug, directly related to the fat content of the meal. Co-administration of food was also found to result in both delayed and enhanced absorption of dihydroartemisinin (ratio between AUC values from time zero to infinity in the fed and states [AUC∞ FED/AUC∞ FASTED] = 142 %, 90 % CI 113–178 %; ratio between mean transit time [MTT] values in the fed and fasted states [MTTFED/MTTFASTED] = 135 %, 90 % CI 114–160 %). CONCLUSION Although food was found to significantly impact on the pharmacokinetics of piperaquine and dihydroartemisinin, given the low fat content of standard meals within endemic regions and the anorexic effects of malaria infection, these results are unlikely to impact on the clinical utility of these drugs. However, co-administration of food with these anti-malarials by populations consuming a typical Western diet should be avoided to reduce the risk of toxic side effects. It is therefore a general recommendation that piperaquine–dihydroartemisinin not be administered within ±3 h of food consumption.
Keywords: Humans; Artemisinins; Quinolines; Antimalarials; Fasting; Area Under Curve; Biological Availability; Energy Intake; Food-Drug Interactions; Food; Adolescent; Adult; Male; Young Adult
Rights: © Springer International Publishing Switzerland 2015
RMID: 0030035378
DOI: 10.1007/s40261-015-0312-8
Appears in Collections:Medicine publications

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