Karin Vos1, Carlotta Lo Sciuto1, Rita Piedade1, Michael Ashton2, Anders Björkman3, Billy Ngasala4, Andreas Mårtensson5, José Pedro Gil1,6. 1. Drug Resistance Unit, Division of Pharmacogenetics, Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden. 2. Unit for Pharmacokinetics & Drug Metabolism, Department of Pharmacology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. 3. Malaria Research Unit, Department of Microbiology, Tumour & Cell biology, Karolinska Institutet, Stockholm, Sweden. 4. Department of Parasitology, Muhimbili University of Health & Allied Sciences, Dar-es-Salaam, Tanzania. 5. Department of Women's & Children's Health, International Maternal & Child Health (IMCH), Uppsala University, Uppsala, Sweden. 6. Center for Biodiversity, Functional & Integrative Genomics, Faculdade de Ciências, Universidade de Lisboa, Portugal.
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.
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/ABCB1C3435T and MRP2/ABCC2C1515Y 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/ABCB1C3435T was found. CONCLUSION:LUM body disposition may be influenced by MRP2/ABCC2 genotype.
Authors: Sa'ad T Abdullahi; Julius O Soyinka; Adeniyi Olagunju; Rahman A Bolarinwa; Olusola J Olarewaju; Moji T Bakare-Odunola; Markus Winterberg; Joel Tarning; Andrew Owen; Saye Khoo Journal: J Clin Pharmacol Date: 2019-09-23 Impact factor: 3.126