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    Variability in the Metabolism of Proguanil to the Active Metabolite Cycloguanil in Healthy Kenyan Adults

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    Publication Date
    1990-08-01
    Authors
    Watkins, W.M.
    Mberu, E.K.
    Nevill, C.G.
    Ward, S.A.
    Breckenridge, A.M.
    Koech, D.K.
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    (6 total)
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    Book chapter
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    Citation

    Watkins WM, Mberu EK, Nevill CG, Ward SA, Breckenridge AM, Koech DK. Variability in the metabolism of proguanil to the active metabolite cycloguanil in healthy Kenyan adults. Trans R Soc Trop Med Hyg. 1990 Jul-Aug;84(4):492-5. doi: 10.1016/0035-9203(90)90010-c. PMID: 2091335.

    Abstract/Overview

    Extensive metabolizers (EM) and poor metabolizers (PM) of the malaria chemoprophylactic drug proguanil have been identified by measuring the proguanil/cycloguanil ratio in urine following a single dose of the pro-drug. The pharmacokinetic characteristics of proguanil were similar in 8 EM and 8 PM subjects, but there were significant differences between the 2 groups with respect to cycloguanil pharmacokinetics. In none of the PM subjects could cycloguanil be detected in whole blood samples at any time after proguanil dosage. Plasma cycloguanil was measureable in only 2 of 8 PM subjects, despite an analytical sensitivity in the high-performance liquid chromatographic assay of 1 ng/ml cycloguanil. A comparatively high proportion of Black Kenyan adults appear to metabolize proguanil poorly, possibly because they lack the specific mixed function oxidase which will accept proguanil as substrate.

    Subject/Keywords
    Extensive metabolizers (EM); Poor metabolizers (PM); Malaria; Chemoprophylactic drug; Pharmacokinetic
    Further Details

    Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 84, Issue 4, July-August 1990, Pages 492–495

    Publisher
    Oxford University Press
    Permalink
    http://repository.amref.org/handle/123456789/195
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    • Book Chapters [14]

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