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  • Title: Influence of debrisoquin phenotype on the inducibility of propranolol metabolism.
    Author: Shaheen O, Biollaz J, Koshakji RP, Wilkinson GR, Wood AJ.
    Journal: Clin Pharmacol Ther; 1989 Apr; 45(4):439-43. PubMed ID: 2702801.
    Abstract:
    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.
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