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  • Title: Defective metabolism of metoprolol in poor hydroxylators of debrisoquine.
    Author: Lennard MS, Silas JH, Freestone S, Trevethick J.
    Journal: Br J Clin Pharmacol; 1982 Aug; 14(2):301-3. PubMed ID: 6125207.
    Abstract:
    Eight healthy volunteers received oral metoprolol 200 mg once daily for a week. The AUC, half-life and duration of beta-adrenoceptor blockade on day 7 was much greater in two subjects than in the remaining six. This suggested that the metabolism of metoprolol was impaired in two and the effect was therefore prolonged. Subsequent testing of oxidation phenotype with oral debrisoquine showed that the subjects with high metoprolol availability were also poor hydroxylators of debrisoquine. The urinary debrisoquine/4-hydroxydebrisoquine ratio was highly correlated with metoprolol AUC, half-life and beta-adrenoceptor blockade at 24 h. Thus patients with a genetic defect in drug oxidation, when treated with metoprolol, are likely to have high plasma concentrations and a prolonged effect.
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