The effects of beta‐adrenoceptor antagonists and levomepromazine on the metabolic ratio of debrisoquine.

The in vivo inhibitory effect of five beta‐adrenoceptor antagonists and levomepromazine on debrisoquine metabolism was assessed in 37 subjects. The debrisoquine phenotyping test was performed before and after 7 days' treatment with oxprenolol (40 mg three times daily), propranolol (20 mg three times daily), timolol (10 mg twice daily), pindolol (5 mg twice daily), metoprolol (50 mg twice daily) or levomepromazine (10 mg daily), each of which was given to six‐seven subjects. No clear change in the urinary metabolic ratio of debrisoquine/4‐OH‐debrisoquine (MR) was seen with any of the single beta‐adrenoceptor antagonist treatments, but the MR value increased significantly when all beta‐ adrenoceptor blocker treatments were considered together. Debrisoquine metabolism was clearly impaired after levomepromazine 10 mg daily for 7 days; the mean MR increased from 1.24 +/− 1.6 to 4.70 +/− 5.23 (P = 0.018) and the excretion of 4‐hydroxydebrisoquine decreased from 0.92 +/− 0.46 mg to 0.31 +/− 0.19 mg (P = 0.043). Thus, levomepromazine changes MRs towards those characteristic of phenotypically poor metabolizers, but beta‐adrenoceptor antagonists at the doses examined have only a marginal effect.