On the population pharmacokinetics and the enterohepatic recirculation of total ezetimibe
| Autor: | Konstantina Soulele, Vangelis Karalis |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male medicine.drug_class Health Toxicology and Mutagenesis Population Administration Oral Population pharmacokinetics Pharmacology Toxicology 030226 pharmacology & pharmacy Biochemistry Bioequivalence study 03 medical and health sciences 0302 clinical medicine Ezetimibe Pharmacokinetics Enterohepatic Circulation medicine Humans Distribution (pharmacology) Cholesterol absorption inhibitor education education.field_of_study Dose-Response Relationship Drug Chemistry Healthy subjects General Medicine 030220 oncology & carcinogenesis Female medicine.drug |
| Zdroj: | Xenobiotica. 49:446-456 |
| ISSN: | 1366-5928 0049-8254 |
| DOI: | 10.1080/00498254.2018.1463117 |
| Popis: | Ezetimibe is a potent cholesterol absorption inhibitor, with an erratic pharmacokinetic (PK) profile, attributed to an extensive enterohepatic recirculation (EHC). The aim of this study was to develop a population PK model able to adequately characterize the complex distribution processes of total ezetimibe. The analysis was performed on the individual concentration-time data obtained from 28 healthy subjects who participated in a bioequivalence study comparing two oral ezetimibe formulations. The population PK analysis was performed using nonlinear mixed effect modeling, where different EHC models were developed and evaluated for their performance. Total ezetimibe pharmacokinetics was best described by a four-compartment model featuring EHC through the inclusion of an additional gallbladder compartment, which was assumed to release drug at specific time-intervals consistent with food intake. The final PK model was able to adequately estimate the population pharmacokinetic parameters and to allow for a formal characterization of the pharmacokinetic profile and the secondary peaks due to enterohepatic recirculation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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