MRP2/ABCC2 C1515Y polymorphism modulates exposure to lumefantrine during artemether-lumefantrine antimalarial therapy. (July 2017)

• Record Type: Journal Article
• Authors: Vos, Karin; Sciuto, Carlotta Lo; Piedade, Rita; Ashton, Michael; Björkman, Anders; Ngasala, Billy; Mårtensson, Andreas; Gil, José Pedro
• Is Part Of: Pharmacogenomics. Volume 18:Number 10(2017)
• Page Start: 981
• Page End: 985
• Publication Date: 2017-07
• Subjects: ABCC2/MRP2 -- ACT -- artemether -- Coartem® -- disposition -- lumefantrine -- malaria; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2017-0032
• Languages: English
• ISSNs: 1462-2416

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 (D7 ) LUM levels were measured.Results: The 1515YY genotype was significantly associated with higher (p < 0.01) LUM D7 concentrations (median 1.42 μM), compared with 0.77 μM for 1515CY and 0.59 μM for 1515CC. No significant influence of the MDR1/ABCB1 C3435T was found.Conclusion: LUM body disposition may be influenced by MRP2/ABCC2 genotype.