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

Abstract

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.

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