Stimulatory as well as inhibitory effects of ethinyloestradiol on the metabolic clearances of propranolol in young women.

1. The metabolism of a single 80 mg oral dose of propranolol was determined in nine young women before and after administration of ethinyloestradiol alone (EE2) or in combination with norethindrone (OC). 2. Whereas the total clearance of propranolol (2713 +/- 404 ml min-1 (mean +/- s.e.mean)) was not significantly altered by either EE2 (3365 +/- 347 ml min-1) or the combined OC (2905 +/- 345 ml min-1), significant changes in all three primary metabolic pathways were observed. 3. The clearance through side-chain oxidation decreased from 345 +/- 55 ml min-1 to 262 +/- 33 ml min-1 after EE2 (P < 0.05). A similar reduction of cytochrome P450 metabolism by EE2 has been observed for other drugs. 4. The clearance through glucuronidation increased from 364 +/- 61 ml min-1 to 625 +/- 117 ml min-1 after EE2 (P < 0.01). Similar stimulation of glucuronic acid conjugation by EE2 has also been observed for other drugs. 5. The clearance through ring oxidation increased from 697 +/- 109 ml min-1 to 1280 +/- 162 ml min-1 after EE2 (P < 0.01). This observation appears to be a novel finding with EE2 and cytochrome P450 metabolism. 6. The treatment with OC produced changes in propranolol's metabolic clearances which were qualitatively similar to those generated by EE2.