title: Influence of debrisoquin phenotype on the inducibility of propranolol metabolism.
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.
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: O
authors.initials: O
authors.lastname: Shaheen
authors.forename: J
authors.initials: J
authors.lastname: Biollaz
authors.forename: R P
authors.initials: RP
authors.lastname: Koshakji
authors.forename: G R
authors.initials: GR
authors.lastname: Wilkinson
authors.forename: A J
authors.initials: AJ
authors.lastname: Wood
mesh_terms: D000328:Adult; D003647:Debrisoquin / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005965:Glucuronates / Q000652:urine; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010641:Phenotype; D011433:Propranolol / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D005965:Glucuronates; D007546:Isoquinolines; C001422:4-hydroxypropranolol; D011433:Propranolol; D006899:Mixed Function Oxygenases; D003647:Debrisoquin