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

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.

Keywords: ABCC2/MRP2; ACT; Coartem®; artemether; disposition; lumefantrine; malaria.