Document Detail


Influence of albumin on isoprenaline and propranolol effects on isolated rat uterus.
MedLine Citation:
PMID:  8251617     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the effect of albumin (6%) on the (+/-)-isoprenaline-induced relaxation of strips of isolated rat uterus and its antagonism by (-)-propranolol. The mean isoprenaline EC50 in the presence of albumin was significantly less than that in the absence of albumin (geometric mean 1.94 +/- 3.33 versus 3.21 +/- 3.50 nM, respectively; n = 14; p = 0.006, paired t test). This indicates enhancement of isoprenaline activity by albumin which could not be explained by protein binding, as this would have reduced activity. Geometric mean control KB values for inhibition of isoprenaline by propranolol at 26.8 and 500 nM were 0.835 +/- 1.68 (n = 10) and 0.889 +/- 1.60 nM (n = 34), respectively. In the presence of 6% albumin, KB for propranolol was increased significantly to 13.3 +/- 1.8 nM (n = 27, p < 0.001). Calculation of KB in terms of the measured propranolol unbound concentration of 26.8 nM, after taking into account the lower isoprenaline EC50 in the presence of albumin, yielded a mean value of 0.725 +/- 1.86 nM, which was not significantly different from either control (p > 0.05). Therefore, propranolol activity was as predicted by the unbound drug concentration in contrast to isoprenaline activity. We conclude that albumin can alter in vitro drug activity by mechanisms in addition to the reduction of unbound drug concentration.
Authors:
D J Morgan; B H Richmond; E Malta
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Biopharmaceutics & drug disposition     Volume:  14     ISSN:  0142-2782     ISO Abbreviation:  Biopharm Drug Dispos     Publication Date:  1993 Oct 
Date Detail:
Created Date:  1994-01-11     Completed Date:  1994-01-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7911226     Medline TA:  Biopharm Drug Dispos     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  627-33     Citation Subset:  IM    
Affiliation:
Victorian College of Pharmacy, Monash University, Melbourne, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dose-Response Relationship, Drug
Female
Isoproterenol / antagonists & inhibitors,  pharmacology*
Kinetics
Muscle Relaxation / drug effects
Propranolol / metabolism,  pharmacology*
Protein Binding
Rats
Rats, Sprague-Dawley
Serum Albumin, Bovine / metabolism,  pharmacology*
Uterine Contraction / drug effects*
Uterus / drug effects,  metabolism,  physiology*
Chemical
Reg. No./Substance:
0/Serum Albumin, Bovine; 525-66-6/Propranolol; 7683-59-2/Isoproterenol

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


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