The metabolism of glyburide in subjects of known debrisoquin phenotype

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Abstract
Ten normal subjects of known debrisoquin phenotype (six extensive (EM) and four poor (PM) metabolizers) were given of 5 mg glyburide (glibenclamide) suspension orally. Plasma glyburide and urinary cis-3-hydroxy-(30H) and trans-4-hydroxyglyburide (40H) were measured by a sensitive HPLC assay. No unchanged glyburide was detected in urine but both metabolites were identified in urine in all subjects. There were no significant differences in any respect with regard to glyburide metabolism or pharmacokinetics between EM and PM of debrisoquin. Estimated mean elimination half-life of glyburide was 3.3 .+-. 1.1 hours for EM and 2.5 .+-. 0.4 hours for PM. In one subject (EM), with reduced excretion of 30H, glyburide was detected in plasma at 24 and 30 hours and the apparent elimination half-life was 9.3 hours. There was no significant difference for total metabolite recovery between EM and PM. Eight of the subjects (six EM and two PM) had previously taken part in a study of tolbutamide metabolism, and a comparison of metabolic clearances by hydroxylation for the two sulfonylureal drugs showed no significant correlation. Glyburide is therefore unlikely to be metabolized by the enzymes that metabolize either debrisoquin or tolbutamide.