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Propranolol metabolism in normal subjects: Association with sex steroid hormones
Author(s) -
Walle Thomas,
Walle U Kristina,
Mathur Rajesh S,
Palesch Yuko Y,
Conradi Edward C
Publication year - 1994
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.1994.115
Subject(s) - propranolol , testosterone (patch) , endocrinology , medicine , hormone , metabolism , pharmacokinetics , steroid , chemistry
The objective of this study was to determine the potential role of circulating testosterone and estradiol in regulation of the activity of the sex‐dependent pathways of propranolol metabolism (i.e., α‐naphthoxylactic acid and propranolol glucuronide). The pharmacokinetics of a single 80 mg oral dose of propranolol and the plasma levels of the sex steroid hormones were therefore determined in normal volunteers. In 33 young men there was a positive correlation between the testosterone levels and the propranolol clearances through both α‐naphthoxylactic acid ( p < 0.001) and propranolol glucuronide ( p < 0.002), as well as the total clearance ( p < 0.05), but not through aromatic ring hydroxylation. Testosterone cypionate administration led to an increased clearance of propranolol through α‐naphthoxylactic acid in nine of the 11 men studied, further supporting a stimulatory effect of testosterone on propranolol metabolism. In 23 young women there was no significant association between the circulating levels of either estradiol or testosterone and any of the clearances of propranolol. These observations may be clinically relevant for propranolol therapy and may provide improved insight into the influence of gender and circulating gonadal hormones on drug metabolism in humans. Clinical Pharmacology and Therapeutics (1994) 56, 127–132; doi: 10.1038/clpt.1994.115