1. MRP2/ABCC2 C1515Y polymorphism modulates exposure to lumefantrine during artemether-lumefantrine antimalarial therapy
- Author
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Vos, Karin, Lo Sciuto, Carlotta, Piedade, Rita, Ashton, Michael, Björkman, Anders, Ngasala, Billy, Mårtensson, Andreas, Gil, Jose Pedro, Vos, Karin, Lo Sciuto, Carlotta, Piedade, Rita, Ashton, Michael, Björkman, Anders, Ngasala, Billy, Mårtensson, Andreas, and Gil, Jose Pedro
- 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.
- Published
- 2017
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