Development of a joint population pharmacokinetic model of ezetimibe and its conjugated metabolite
| Autor: | Vangelis Karalis, Konstantina Soulele |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Metabolite Drug Compounding Population Pharmaceutical Science 02 engineering and technology Pharmacology Conjugated system 030226 pharmacology & pharmacy Models Biological 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glucuronides Pharmacokinetics Ezetimibe medicine Humans education Hypolipidemic Agents education.field_of_study Healthy subjects 021001 nanoscience & nanotechnology chemistry Mixed effects Azetidines 0210 nano-technology Glucuronide medicine.drug |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 128 |
| ISSN: | 1879-0720 |
| Popis: | Ezetimibe (EZE) is an extensively used antihyperlipidemic drug with an important cholesterol lowering activity. It undergoes extensive first-pass metabolism to form its active glucuronide metabolite (EZEG). Both drugs exhibit complex pharmacokinetic profiles attributed mainly to repetitive enterohepatic kinetics. The aim of the present study was the investigation of EZE and EZEG pharmacokinetics (PK), through the development of a joint population pharmacokinetic model able to characterize their kinetic processes and enterohepatic recirculation simultaneously. Concentration-time data derived from a bioequivalence study in 28 healthy subjects were used for the analysis. Population PK modeling was performed on the obtained data using nonlinear mixed effect modeling approach, where different methodologies were applied for the description of the complex metabolism and recirculation processes of the two compounds. EZE and EZEG concentrations were best described by a population PK model incorporating first-pass metabolism and an enterohepatic recirculation loop, accounting for the recycling process of the two moieties. This is the first joint population pharmacokinetic model describing the kinetics of both EZE and EZEG. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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