Document Detail


Neonatal hepatic propranolol elimination: studies in the isolated perfused neonatal sheep liver.
MedLine Citation:
PMID:  10756324     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Using the isolated perfused neonatal sheep liver model, we examined the disposition of propranolol (n = 8, age 0.25-10 days) and compared our findings with our previous study from the perfused near-term fetal sheep liver (Ring JA, et al. 1995. Drug Metab Dispos 23:190-196). Within 45 min of dosage, perfusate propranolol levels had fallen by three orders of magnitude to be less than the limit of detection. Perfusate disappearance curves were monoexponential in six experiments and biexponential in two experiments. The mean shunt-corrected hepatic extraction ratio was 0.92 +/- 0.09, much greater than that seen in the fetal sheep liver (0.26 +/- 0.13, P < 0.0001) but still less than values in the adult sheep (0.97). At the conclusion of the perfusion, 4-hydroxypropranolol was the major metabolite present and 5-hydroxypropranolol and N-desisopropylpropranolol were minor metabolites. We conclude that the isolated perfused neonatal sheep liver is a useful model with which to study the maturation of neonatal hepatic drug oxidation. Our study shows that propranolol is rapidly eliminated by the neonatal liver to form several metabolites at rates far greater than in the fetal liver, but rates of elimination have not yet reached that reported in the adult sheep liver.
Authors:
P J Gow; S Treepongkaruna; H Ghabrial; A Shulkes; R A Smallwood; D J Morgan; M S Ching
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  89     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-07-28     Completed Date:  2000-07-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  586-93     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Wiley-Liss Inc.
Affiliation:
Department of Medicine, Austin and Repatriation Medical Centre, West Heidelberg, Victoria 3081, Australia.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / metabolism,  pharmacokinetics*
Animals
Animals, Newborn
Liver / metabolism*
Perfusion
Propranolol / metabolism,  pharmacokinetics*
Sheep
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 525-66-6/Propranolol

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


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