Document Detail


Bile flow but not enterohepatic recirculation influences the pharmacokinetics of ranitidine in the rat.
MedLine Citation:
PMID:  8013278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Secondary peaks in oral concentration-time profiles following ranitidine administration may be due to discontinuous absorption along the gastrointestinal tract, postabsorptive storage and release, and/or enterohepatic recirculation (ER). The suitability of the rat as an animal model for studying mechanisms of the double peaks, and the relationship between ER and the occurrence of secondary peaks in ranitidine concentration-time profiles, were examined in the present investigation. Male Sprague-Dawley rats received ranitidine by oral gavage (50 mg/kg), and blood was collected at various times for 6 hr after dosing. Eight rats with chronic bile duct and jugular vein cannulae received ranitidine with bile flow intact or interrupted in a randomized complete cross-over design. Bile duct-cannulated (BDC) rats were divided into two groups: four rats received ranitidine immediately after bile flow interruption, and four rats received ranitidine 3 hr after bile flow interruption. Blood and bile were analyzed for ranitidine by HPLC. The area under the ranitidine concentration-time profile, the maximum serum ranitidine concentration, the time of maximum concentration, the fraction of ranitidine absorbed at each blood sample, biliary clearance, and the percentage of the dose recovered in bile as ranitidine were determined. Results indicated that the rat is an appropriate model for studying mechanisms responsible for the double peaking phenomenon. Multiple peaks or plateaus were observed in the ranitidine concentration-time profiles of all rats after oral administration with bile flow intact. Secondary peaks were evident in only two concentration-time profiles of BDC rats when bile flow was interrupted. Less than 3% of the dose was recovered in the bile as ranitidine or metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
A B Suttle; K L Brouwer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  22     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:    1994 Mar-Apr
Date Detail:
Created Date:  1994-07-26     Completed Date:  1994-07-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  224-32     Citation Subset:  IM    
Affiliation:
Division of Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill 27599-7360.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bile / physiology*
Biliary Tract / physiology
Biotransformation
Dealkylation
Enterohepatic Circulation / physiology*
Intestinal Absorption
Male
Models, Biological
Oxidation-Reduction
Ranitidine / blood,  pharmacokinetics*
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
66357-35-5/Ranitidine

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


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