Document Detail

Interaction of phenobarbital with propranolol in the dog. 3. Beta blockade.
MedLine Citation:
PMID:  6129320     Owner:  NLM     Status:  MEDLINE    
The chronic administration of phenobarbital (180 mg/day p.o.) alters the binding, bioavailability, metabolism and pharmacokinetics of propranolol. Consequently, phenobarbital affects the pharmacological activity of propranolol as measured by inhibition of isoproterenol tachycardia in dogs. Altered binding affects beta blockade in two ways; a reduction in the free fraction and the volume of distribution. To separate the effects of active metabolites from the parent drug, we have used an integrated form of the equation (DR -- 1) = K.(p), where DR is the dose ratio and p is the concentration of the free (unbound) propranolol in plasma. The activity due to propranolol itself is subtracted from the total observed amount of beta blockade. In this way, phenobarbital was shown to increase the amount of beta blockade which was due to active metabolites. Phenobarbital treatment shortened the time course of beta blockade. The beta blocking half-life for propranolol followed its pharmacokinetic half-life closely for a variety of experimental conditions. This suggests that pharmacological activity data could be used to describe pharmacokinetics without measuring blood concentrations.
S A Bai; F P Abramson
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  224     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1983 Jan 
Date Detail:
Created Date:  1983-02-14     Completed Date:  1983-02-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  62-7     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Administration, Oral
Adrenergic beta-Antagonists*
Drug Interactions
Infusions, Parenteral
Isoproterenol / antagonists & inhibitors
Phenobarbital / pharmacology*
Propranolol / metabolism,  pharmacology*
Grant Support
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 50-06-6/Phenobarbital; 525-66-6/Propranolol; 7683-59-2/Isoproterenol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The effects of a beta-2 selective adrenergic receptor antagonist (ICI 118,551) on twitch tension in ...
Next Document:  U-50,488: a selective and structurally novel non-Mu (kappa) opioid agonist.