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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Effects of genetic variation at the CYP2C19/CYP2C9 locus on pharmacokinetics of chlorcycloguanil in adult Gambians
Pharmacogenomics, Volume 10, No. 9, Year 2009
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Description
Aims: Antimalarial biguanides are metabolized by CYP2C19, thus genetic variation at the CYP2C locus might affect pharmacokinetics and so treatment outcome for malaria. Materials & methods: Polymorphisms in CYP2C19 and CYP2C9 in 43 adult Gambians treated with chlorproguanil/dapsone for uncomplicated malaria were assessed. Chlorcycloguanil pharmacokinetics were measured and associations with CYP2C19 and CYP2C9 alleles and CYP2C19 metabolizer groups investigated. Results: All CYP2C19/CYP2C9 alleles obeyed Hardy-Weinberg equilibrium. There were 15 CYP2C19/2C9 haplotypes with a common haplotype frequency of 0.23. Participants with the CYP2C19*17 allele had higher chlorcycloguanil area under the concentration versus curve at 24 h (AUC0-24) than those without (geometric means: 317 vs 216 ng.h/ml; ratio of geometric means: 1.46; 95% CI: 1.03 to 2.09; p = 0.0363) and higher Cmax (geometric mean ratio: 1.52; 95% CI: 1.13 to 2.05; p = 0.0071). Conclusion: CYP2C19*17 determines antimalarial biguanide metabolic profile at the CYP2C19/CYP2C9 locus. © 2009 Future Medicine Ltd.
Authors & Co-Authors
Janha, Ramatoulie E.
Unknown Affiliation
Sisay-Joof, Fatoumatta
Unknown Affiliation
Hamid-Adiamoh, Majidah
Unknown Affiliation
Worwui, Archibald Kwame
Unknown Affiliation
Chapman, Hannah L.
Unknown Affiliation
Opara, Hyginus
Unknown Affiliation
Dunyo, Samuel K.
Unknown Affiliation
Milligan, Paul J.M.
Unknown Affiliation
Rockett, Kirk A.
Unknown Affiliation
Winstanley, Peter A.
Unknown Affiliation
Pirmohamed, Munir
Unknown Affiliation
Miller, Ann
Unknown Affiliation
Conway, David J.
Unknown Affiliation
Walton, Robert T.
Unknown Affiliation
Statistics
Citations: 20
Authors: 14
Affiliations: 7
Identifiers
Doi:
10.2217/pgs.09.72
ISSN:
14622416
e-ISSN:
17448042
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases
Noncommunicable Diseases