Mechanisms for large variations in rates of elimination of the model compound antipyrine (AP) were investigated by administering AP to 144 normal, uninduced subjects (83 unrelated adults and 61 members of 13 families). Urine was collected at regular intervals for 72 h and concentrations of AP and its three main metabolites were measured. Rate constants for formation of each AP metabolite were calculated. When values for each AP rate constant were plotted arithmetically for 83 unrelated subjects, trimodal curves emerged. Probit plots of these values showed inflections at the two antimodes of each trimodal distribution. Members of all 13 families were assigned a phenotype determined by where their AP metabolite rate constant placed them in the trimodal distributions derived from unrelated subjects. In each family, pedigree analysis to test a Mendelian hypothesis for transmission of these three phenotypes was consistent with their monogenic control for each AP metabolite. The same two-step procedure used here for AP offers a general approach for identifying other polymorphisms of drug oxidation. This method consists of constructing distribution curves for unrelated subjects, which allow the phenotypes of families to be determined so that segregation patterns can then be traced.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Jan 1 1984|
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