Goncalves , B P , Pett , H , Tiono , A B , Murry , D , Sirima , S B , Niemi , M , Bousema , T , Drakeley , C & ter Heine , R 2017 , ' Age, Weight, and CYP2D6 Genotype Are Major Determinants of Primaquine Pharmacokinetics in African Children ' , Antimicrobial Agents and Chemotherapy , vol. 61 , no. 5 , 02590 . https://doi.org/10.1128/AAC.02590-16
Title: | Age, Weight, and CYP2D6 Genotype Are Major Determinants of Primaquine Pharmacokinetics in African Children |
Author: | Goncalves, Bronner P.; Pett, Helmi; Tiono, Alfred B.; Murry, Daryl; Sirima, Sodiomon B.; Niemi, Mikko; Bousema, Teun; Drakeley, Chris; ter Heine, Rob |
Contributor organization: | Clinicum University of Helsinki Department of Clinical Pharmacology Medicum HUSLAB |
Date: | 2017-05 |
Language: | eng |
Number of pages: | 11 |
Belongs to series: | Antimicrobial Agents and Chemotherapy |
ISSN: | 0066-4804 |
DOI: | https://doi.org/10.1128/AAC.02590-16 |
URI: | http://hdl.handle.net/10138/203372 |
Abstract: | Low-dose primaquine is recommended to prevent Plasmodium falciparum malaria transmission in areas threatened by artemisinin resistance and areas aiming for malaria elimination. Community treatment campaigns with artemisinin-based combination therapy in combination with the gametocytocidal primaquine dose target all age groups, but no studies thus far have assessed the pharmacokinetics of this gametocytocidal drug in African children. We recruited 40 children participating in a primaquine efficacy trial in Burkina Faso to study primaquine pharmacokinetics. These children received artemether-lumefantrine and either a 0.25- or a 0.40-mg/kg primaquine dose. Seven blood samples were collected from each participant for primaquine and carboxy-primaquine plasma levels determinations: one sample was collected before primaquine administration and six after primaquine administration according to partially overlapping sampling schedules. Physiological population pharmacokinetic modeling was used to assess the impact of weight, age, and CYP2D6 genotype on primaquine and carboxy-primaquine pharmacokinetics. Despite linear weight normalized dosing, the areas under the plasma concentration-time curves and the peak concentrations for both primaquine and carboxy-primaquine increased with age and body weight. Children who were CYP2D6 poor metabolizers had higher levels of the parent compound, indicating a lower primaquine CYP2D6-mediated metabolism. Our data indicate that primaquine and carboxy-primaquine pharmacokinetics are influenced by age, weight, and CYP2D6 genotype and suggest that dosing strategies may have to be reconsidered to maximize the transmission-blocking properties of primaquine. |
Subject: |
pharmacokinetics
primaquine Plasmodium falciparum CYP2D6 PLASMODIUM-VIVAX MALARIA SINGLE-DOSE PRIMAQUINE NEW-GUINEAN CHILDREN ARTEMETHER-LUMEFANTRINE DIHYDROARTEMISININ-PIPERAQUINE UNCOMPLICATED MALARIA FALCIPARUM-MALARIA CONTROLLED-TRIAL RADICAL CURE DOUBLE-BLIND 3111 Biomedicine 3123 Gynaecology and paediatrics |
Peer reviewed: | Yes |
Rights: | cc_by |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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