A Physiologically Based Pharmacokinetic and Pharmacodynamic Model of the CYP3A4 Substrate Felodipine for Drug-Drug Interaction Modeling.

cytochrome P450 3A4 (CYP3A4) drug–drug interactions (DDIs) felodipine pharmacodynamics physiologically based pharmacokinetic (PBPK) modeling

Journal

Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003

Informations de publication

Date de publication:
15 Jul 2022
Historique:
received: 14 06 2022
revised: 12 07 2022
accepted: 13 07 2022
entrez: 27 7 2022
pubmed: 28 7 2022
medline: 28 7 2022
Statut: epublish

Résumé

The antihypertensive felodipine is a calcium channel blocker of the dihydropyridine type, and its pharmacodynamic effect directly correlates with its plasma concentration. As a sensitive substrate of cytochrome P450 (CYP) 3A4 with high first-pass metabolism, felodipine shows low oral bioavailability and is susceptible to drug-drug interactions (DDIs) with CYP3A4 perpetrators. This study aimed to develop a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) parent-metabolite model of felodipine and its metabolite dehydrofelodipine for DDI predictions. The model was developed in PK-Sim

Identifiants

pubmed: 35890369
pii: pharmaceutics14071474
doi: 10.3390/pharmaceutics14071474
pmc: PMC9322514
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Federal Ministry of Education and Research
ID : 031L0161C

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Auteurs

Laura Maria Fuhr (LM)

Department of Clinical Pharmacy, Saarland University, 66123 Saarbrücken, Germany.

Fatima Zahra Marok (FZ)

Department of Clinical Pharmacy, Saarland University, 66123 Saarbrücken, Germany.

Maximilian Mees (M)

Department of Clinical Pharmacy, Saarland University, 66123 Saarbrücken, Germany.

Felix Mahfoud (F)

Department of Internal Medicine III (Cardiology, Angiology, Intensive Care Medicine), Saarland University Medical Center and Saarland University Faculty of Medicine, 66421 Homburg, Germany.
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Dominik Selzer (D)

Department of Clinical Pharmacy, Saarland University, 66123 Saarbrücken, Germany.

Thorsten Lehr (T)

Department of Clinical Pharmacy, Saarland University, 66123 Saarbrücken, Germany.

Classifications MeSH