Influence of debrisoquin phenotype on the inducibility of propranolol metabolism

The effects of rifampin (600 mg) once daily for 22 days on the total and fractional metabolic clearances of propranolol were determined in a group of six genetically extensive (EM) and six poor metabolizers (PM) of debrisoquin. The impaired ability of PMs to metabolize propranolol to the ring-oxidized metabolite 4-hydroxypropranolol was confirmed. The total oral clearance of propranolol increased about fourfold in both phenotypes from 219.2 +/- 52.8 to 976.7 L/hr in the EMs and from 75.0 +/- 12.6 to 289.8 +/- 78.2 L/hr in the PMs. The extent of induction of glucuronidation was similar in the two groups. 4-Hydroxylation was induced in both phenotypes but the increase was fifteenfold greater in EMs than in PMs. This would imply that the cytochrome P-450 determined by the debrisoquin allele or some coinherited 4-hydroxylase(s) was induced to a greater extent in EMs than PMs.