Document Detail


Intestinal permeability and excretion into bile control the arrival of amlodipine into the systemic circulation after oral administration.
MedLine Citation:
PMID:  16734984     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The objective of this study was to identify the factors controlling the arrival of amlodipine into the systemic circulation after oral administration in the fasting state. Dissolution data were collected with the rotating paddle and the flow-through apparatus. Caco-2 cell lines were used to assess the intestinal permeability characteristics. Actual in-vivo data were collected in 24 fasted healthy subjects after single-dose administration of the same amlodipine besylate tablet formulation used in the in-vitro dissolution studies. Regardless of the hydrodynamics, dissolution of amlodipine besylate tablets was rapid and complete in media simulating the contents of the upper gastrointestinal tract in the fasting state. Permeability of amlodipine through Caco-2 cell lines was lower than propranolol's and higher than ranitidine's, indicating that transport through the intestinal mucosa may be one process that limits the arrival into the systemic circulation. Indeed, the de-convoluted profile indicated that arrival into portal blood occurs at rates much slower than gastric emptying or dissolution rates. However, prediction of amlodipine's mean plasma profile after oral administration became possible only after additionally assuming excretion of amlodipine into the bile and a reasonable gastrointestinal residence time. Interestingly, in-vitro permeability data collected in this or in previous studies were inappropriate for simulating the mean actual plasma profile.
Authors:
Dragica Rausl; Nikoletta Fotaki; Ruzica Zanoski; Maria Vertzoni; Biserka Cetina-Cizmek; M Zahirul I Khan; Christos Reppas
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  58     ISSN:  0022-3573     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-31     Completed Date:  2006-09-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  827-36     Citation Subset:  IM    
Affiliation:
PLIVA Research and Development Ltd., Prilaz baruna Filipovića 29, 10 000 Zagreb, Croatia.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adult
Amlodipine / administration & dosage,  pharmacokinetics*
Bile / metabolism*
Calcium Channel Blockers / pharmacokinetics*
Humans
Hydrogen-Ion Concentration
Intestines / metabolism*
Membranes, Artificial
Permeability
Solubility
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Membranes, Artificial; 88150-42-9/Amlodipine

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


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