Physiologically motivated time-delay model to account for mechanisms underlying enterohepatic circulation of piroxicam in human beings

Basic & Clinical Pharmacology & Toxicology
Martina TvrdonovaMaria Durisova

Abstract

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...Continue Reading

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Citations

Sep 24, 2011·Expert Opinion on Drug Metabolism & Toxicology·Jennifer B DressmanStefan Willmann
Mar 19, 2016·Drug Metabolism Reviews·Mohd Yaseen MalikJawahar Lal
May 9, 2012·TheScientificWorldJournal·Mária Durišová
Apr 9, 2016·PloS One·Jiraphat YokrattanasakYongwimon Lenbury
Mar 25, 2019·Pharmaceutics·Constantin MircioiuIon Mircioiu
Dec 11, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Ayorinde AdehinWen Tan

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