PROPRANOLOL METABOLISM IN NORMAL SUBJECTS - ASSOCIATION WITH SEX STEROID-HORMONES

The objective of this study was to determine the potential role of cir culating testosterone and estradiol in regulation of the activity of t he sex-dependent pathways of propranolol metabolism (i.e., alpha-napht hoxylactic acid and propranolol glucuronide). The pharmacokinetics of a single 80 mg dose of propranolol and the plasma levels of the sex st eroid hormones were therefore determined in normal volunteers. In 33 y oung men there was a positive correlation between the testosterone lev els and the propranolol clearances through both alpha-naphthoxylactic acid (p < 0.001) and propranolol glucuronide (p < 0.002), as well as t he total clearance (p < 0.05), but not through aromatic ring hydroxyla tion. Testosterone cypionate administration led to an increased cleara nce of propranolol through alpha-naphthoxylactic acid in nine of the 1 1 men studied, further supporting a stimulatory effect of testosterone on propranolol metabolism. In 23 young women there was no significant association between the circulating level of either estradiol or test osterone and any of the clearances of propranolol. These observations may be clinically relevant for propranolol therapy and may provide imp roved insight into the influence of gender and circulating gonadal hor mones on drug metabolism in humans.