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Polymorphic ability to metabolize propranolol alters 4‐hydroxypropranolol levels but not beta blockade
Author(s) -
Raghuram T C,
Koshakji R P,
Wilkinson G R,
Wood A J J
Publication year - 1984
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1984.138
Subject(s) - debrisoquine , propranolol , blockade , metabolite , pharmacology , active metabolite , population , chemistry , significant difference , metabolism , biology , medicine , endocrinology , biochemistry , cyp2d6 , receptor , cytochrome p450 , environmental health
The ability to hydroxylate debrisoquine is known to be polymorphically distributed, with about 8% to 9% of the North American Caucasian population being poor metabolizers. We have shown that the ability to 4‐hydroxylate propranolol is also polymorphically determined and that it cosegregates with ability to metabolize debrisoquine, such that poor debrisoquine metabolizers produce much less 4‐hydroxypropranolol (4‐OH propranolol) than do extensive metabolizers. There was no significant difference, however, between plasma propranolol concentrations after either single or multiple doses in the two groups. Despite the substantial difference in production of the pharmacologically active 4‐OH metabolite, no difference was seen in the extent of β‐blockade induced in the extensive and poor metabolizers, which implies that 4‐OH propranolol does not contribute substantially to β‐blockade. Clinical Pharmacology and Therapeutics (1984) 36, 51–56; doi: 10.1038/clpt.1984.138