Document Detail


Physiologically motivated time-delay model to account for mechanisms underlying enterohepatic circulation of piroxicam in human beings.
MedLine Citation:
PMID:  18713233     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The study was conducted to formulate a physiologically motivated time-delay (PM TD) mathematical model for human beings, which incorporates disintegration of a drug formulation, dissolution, discontinuous gastric emptying and enterohepatic circulation (EHC) of a drug. Piroxicam, administered to 24 European, healthy individuals in 20 mg capsules Feldene Pfizer, was used as a model drug. Plasma was analysed for piroxicam by a validated high-performance liquid chromatography method. The PM TD mathematical model was developed using measured plasma piroxicam concentration-time profiles of the individuals and tools of a computationally efficient mathematical analysis and modeling, based on the theory of linear dynamic systems. The constructed model was capable of (i) quantifying different fractions of the piroxicam dose sequentially disposable for absorption and (ii) estimating time delays between time when the piroxicam dose reaches stomach and time when individual of fractions of the piroxicam dose is disposable for absorption. The model verification was performed through a formal proof, based on comparisons of observed and model-predicted plasma piroxicam concentration-time profiles. The model verification showed an adequate model performance and agreement between the compared profiles. Accordingly, it confirmed that the developed model was an appropriate representative of the piroxicam fate in the individuals enrolled. The presented model provides valuable information on factors that control dynamic mechanisms of EHC, that is, information unobtainable with the models proposed for the EHC analysis previously.
Authors:
Martina Tvrdonova; Ladislav Dedik; Constantin Mircioiu; Daniela Miklovicova; Maria Durisova
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  104     ISSN:  1742-7843     ISO Abbreviation:  Basic Clin. Pharmacol. Toxicol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-26     Completed Date:  2009-03-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  35-42     Citation Subset:  IM    
Affiliation:
Institute of Automation, Measurement and Applied Informatics, Faculty of Mechanical Engineering, Slovak University of Technology, Bratislava, Slovakia.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Anti-Inflammatory Agents, Non-Steroidal / blood,  pharmacokinetics*
Biotransformation
Chromatography, High Pressure Liquid
Enterohepatic Circulation*
Female
Humans
Liver / metabolism*
Male
Mathematics
Middle Aged
Models, Biological*
Piroxicam / blood,  pharmacokinetics*
Time Factors
Young Adult
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 36322-90-4/Piroxicam

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


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