• Login
    View Item 
    •   Mak IR Home
    • College of Health Sciences (CHS)
    • School of Bio-Medical Sciences (Bio-Medical)
    • School of Bio-Medical Sciences (Bio-Medical) Collections
    • View Item
    •   Mak IR Home
    • College of Health Sciences (CHS)
    • School of Bio-Medical Sciences (Bio-Medical)
    • School of Bio-Medical Sciences (Bio-Medical) Collections
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Genetic variations in ABCB1 and CYP3A5 as well as sex influence quinine disposition among Ugandans

    Thumbnail
    View/Open
    Mukonzo-chs-res.pdf (372.5Kb)
    Date
    2010
    Author
    Mukonzo, Jackson K
    Waako, Paul
    Ogwal-Okeng, Jasper
    Gustafsson, Lars L.
    Aklillu, Eleni
    Metadata
    Show full item record
    Abstract
    Abstract: Quinine is one of the most effective antimalarial drugs, although its clinical use is limited as a result of its narrow safety margin. Quinine is a substrate of the polymorphic p-glycoprotein and CYP3A4/3A5. This study aimed to examine the effects of genetic variations in ABCB1 and CYP3A5 genes, sex, demographic, and biochemical variables (serum albumin, creatinine, alanine aminotransferase and albumin) on quinine disposition among Ugandans. Quinine (600 mg) was orally administered to 140 healthy volunteers. Quinine and its metabolite 3-hydroxyquinine concentrations were determined from 16-hour postdose plasma by high-performance liquid chromatography. CYP3A5 activity was measured using quinine/3-hydroxyquinine ratio (metabolic ratio). Genotyping for a total of 20 single nucleotide polymorphisms in ABCB1 (n = 13) and CYP3A5 (n = 7) was done using Taqman and minisequencing on microarray. There were 20.5- and 13-fold variations in body weight adjusted plasma quinine concentrations (mean ± standard deviation, 5.26 ± 2.5 µmol/L; range, 0.88–18.10 µmol/L) and quinine-to-3- hydroxyquinine metabolic ratio (mean ± standard deviation, 7.68 ± 3.3 µmol/L; range, 1.66–22.3 µmol/L), respectively. Weight-adjusted plasma quinine concentration was significantly influenced by sex and ABCB1 haplotype. There was a significant sex difference in quinine metabolic ratio, women being faster metabolizers than men (P = 0.01). CYP3A5 genotype/haplotype significantly (P = 0.03) influenced quinine disposition with a clear CYP3A5*1 gene dose effect. The result confirms that quinine disposition is influenced mainly by sex as well as by ABCB1 and CYP3A5 genotypes. Despite being fast metabolizers, women display higher quinine bioavailability than men in Uganda. This may have clinical significance in determining an individual’s susceptibility to quinine-associated adverse reactions such as cinchonism.
    URI
    http://hdl.handle.net/10570/645
    Collections
    • School of Bio-Medical Sciences (Bio-Medical) Collections

    DSpace 5.8 copyright © Makerere University 
    Contact Us | Send Feedback
    Theme by 
    Atmire NV
     

     

    Browse

    All of Mak IRCommunities & CollectionsTitlesAuthorsBy AdvisorBy Issue DateSubjectsBy TypeThis CollectionTitlesAuthorsBy AdvisorBy Issue DateSubjectsBy Type

    My Account

    LoginRegister

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    DSpace 5.8 copyright © Makerere University 
    Contact Us | Send Feedback
    Theme by 
    Atmire NV