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MRP2/ABCC2 C1515Y polymorphism modulates exposure to lumefantrine during artemether-lumefantrine antimalarial therapy

Journal article
Authors K. Vos
C. Lo Sciuto
R. Piedade
Michael Ashton
A. Bjorkman
B. Ngasala
A. Martensson
J. P. Gil
Published in Pharmacogenomics
Volume 18
Issue 10
Pages 981-985
ISSN 1462-2416
Publication year 2017
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 981-985
Language en
Links 10.2217/pgs-2017-0032
Keywords ABCC2/MRP2, ACT, artemether, Coartem (R), disposition, lumefantrine, malaria, plasmodium-falciparum malaria, pharmacokinetics, children, pharmacodynamics, bioavailability, coartem(r), tanzania, abcc2
Subject categories Pharmacology and Toxicology

Abstract

Aim: To investigate the potential involvement of the hepatic ATP-binding cassette transporters MRP2 and MDR1 in the disposition of lumefantrine (LUM) among patients with uncomplicated Plasmodium falciparum malaria. Materials & methods: The tag SNPs MDR1/ABCB1 C3435T and MRP2/ABCC2 C1515Y were determined in two artemether-LUM clinical trials, including a pharmacokinetic/pharmacodynamic study focused on the treatment phase (72 h), and an efficacy trial where day 7 (D-7) LUM levels were measured. Results: The 1515YY genotype was significantly associated with higher (p < 0.01) LUM D-7 concentrations (median 1.42 mu M), compared with 0.77 mu M for 1515CY and 0.59 mu M for 1515CC. No significant influence of the MDR1/ABCB1 C3435T was found. Conclusion: LUM body disposition may be influenced by MRP2/ABCC2 genotype.

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