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

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Keyword

ABCC2/MRP2

ACT

artemether

Coartem (R)

disposition

lumefantrine

malaria

plasmodium-falciparum malaria

pharmacokinetics

children

pharmacodynamics

bioavailability

coartem(r)

tanzania

abcc2

ABCC2/MRP2

Publication and Content Type

ref (subject category)

art (subject category)