Influence of debrisoquin phenotype on the inducibility of propranolol metabolism.
Details
Serval ID
serval:BIB_61B7032FD7EA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Influence of debrisoquin phenotype on the inducibility of propranolol metabolism.
Journal
Clinical Pharmacology and Therapeutics
ISSN
0009-9236 (Print)
ISSN-L
0009-9236
Publication state
Published
Issued date
1989
Volume
45
Number
4
Pages
439-443
Language
english
Notes
Publication types: Journal Article ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Publication Status: ppublish
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.
Keywords
Adult, Debrisoquin/pharmacology, Enzyme Induction/drug effects, Glucuronates/urine, Humans, Isoquinolines/pharmacology, Male, Metabolic Clearance Rate/drug effects, Mixed Function Oxygenases/metabolism, Phenotype, Propranolol/analogs & derivatives, Propranolol/metabolism
Pubmed
Web of science
Create date
25/01/2008 11:41
Last modification date
20/08/2019 15:18