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

作者：Vos Karin; Lo Sciuto Carlotta; Piedade Rita; Ashton Michael; Bjorkman Anders; Ngasala Billy; Martensson Andreas; Gil Jose Pedro^*

来源：Pharmacogenomics, 2017, 18(10): 981-985.

DOI：10.2217/pgs-2017-0032

• ABCC2/MRP2
• ACT
• artemether
• Coartem (R)
• disposition
• lumefantrine
• malaria

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.

• 出版日期2017-7