Oxidation Phenotype — A Major Determinant of Metoprolol Metabolism and Response

The relationship between debrisoquine oxidation phenotype and the pharmacokinetics and pharmacodynamics of propranolol.

“…Confidence limits for these data are wide and proof of no difference in the oral clearance of propranolol in the two phenotypes would require a study with larger numbers of subjects. On the other hand, large differences in metoprolol AUC between extensive and poor metabolisers of debrisoquine were observed in a study of similar design and size (Lennard et al, 1982b).…”

“…Population studies also suggest that the metabolism of these drugs is under common genetic control (Lennard et al, 1982a(Lennard et al, , b, 1983aDayer et al, 1982Dayer et al, , 1983. Furthermore, there is evidence that metoprolol produces more intense and more prolonged ,8-adrenoceptor blockade in poor metabolisers of debrisoquine than in extensive metabolisers (Lennard et al, 1982b). …”

“…The aim of the present study was to explore the relationship between debrisoquine oxidation phenotype and the pharmacokinetics and pharmacodynamics of propranolol in a panel of healthy volunteers. (Lennard et al, 1982b) and the panel consisted of seven extensive and four poor metabolisers of debrisoquine.…”

Comparison of two slow‐release formulations of metoprolol with conventional metoprolol and atenolol in hypertensive patients.

“…The metabolism of metoprolol exhibits polymorphism of the debrisoquine type with about 9% of the population having the poor metaboliser phenotype, 91% the extensive metaboliser phenotype. Poor metabolisers have substantially higher plasma metoprolol concentrations and longer half-lives compared to extensive metabolisers (Lennard et al, 1982 (Scott et al, 1982;Kierso et al, 1983). The performance of this film-coated preparation is reminiscent of that of similai oxprenolol formulations which have also proved unsatisfactory for once-daily treatment of angina or hypertension (Wilcox & Hampton, 1981;Petrie et al, 1980;Leahey et al, 1980;Bobik et al, 1979).…”

“…Metoprolol metabolism is subject to polymorphism of the debrisoquine type (Lennard et al, 1982. Therefore oxidation phenotype was determined by measuring the ratio of debrisoquine/4-hydroxydebrisoquine (metabolic ratio) in an 8 h urine collection following a 10 mg single oral dose of debrisoquine (Mahgoub et al, 1977;Lennard et al, 1977).…”