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

Karin Vos, and Carlotta Lo Sciuto, and Rita Piedade, and Michael Ashton, and Anders Björkman, and Billy Ngasala, and Andreas Mårtensson, and José Pedro Gil
Drug Resistance Unit, Division of Pharmacogenetics, Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden.

OBJECTIVE 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. 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. CONCLUSIONS LUM body disposition may be influenced by MRP2/ABCC2 genotype.

UI MeSH Term Description Entries
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D004983 Ethanolamines AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives. Aminoethanols
D005449 Fluorenes A family of diphenylenemethane derivatives.
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071184 Pharmacogenomic Variants Naturally occurring genetic variations associated with drug response (e.g., dosage, extent and rate of metabolic processes). While these variants are not markers for GENETIC PREDISPOSITION TO DISEASE they influence PHARMACOKINETICS and pharmacodynamics and often occur on genes encoding drug metabolism enzymes and transporters (e.g., ANGIOTENSIN CONVERTING ENZYME; CYTOCHROME P-450 CYP2D6). Pharmacogenetic Variants,Pharmacokinetic Genetic Variants,Genetic Variant, Pharmacokinetic,Genetic Variants, Pharmacokinetic,Pharmacogenetic Variant,Pharmacogenomic Variant,Pharmacokinetic Genetic Variant,Variant, Pharmacogenetic,Variant, Pharmacogenomic,Variants, Pharmacogenetic,Variants, Pharmacogenomic
D000077549 Artemether An artemisinin derivative that is used in the treatment of MALARIA. Artemether, (3R-(3alpha,5abeta,6alpha,8abeta,9alpha,10beta,12beta,12aR*))-isomer,Artemether, (3R-(3alpha,5abeta,6beta,8aalpha,9alpha,10beta,12beta,12aR*))-isomer,Artemether, (3R-(3alpha,5abeta,6beta,8abeta,9alpha,10alpha,12beta,12aR*))-isomer,Artenam,O-Methyldihydroartemisinine,alpha-Artemether,beta-Arthemeter,O Methyldihydroartemisinine,alpha Artemether,beta Arthemeter
D000078102 Lumefantrine A fluorene derivative that is used in combination with ARTEMETHER for the treatment of MALARIA (see ARTEMETHER-LUMEFANTRINE DRUG COMBINATION). 9H-Fluorene-4-methanol, 2,7-dichloro-9-((4-chlorophenyl)methylene)-alpha-((dibutylamino)methyl)-, (Z)-,Benflumetol,Benflumetol, (+)-isomer,Benflumetol, (+-)-isomer,Benflumetol, (-)-isomer

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