Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions.
Administration, Intravenous
Administration, Oral
Adult
Biotransformation
Computer Simulation
Drug Elimination Routes
Drug Interactions
Female
Furosemide
/ administration & dosage
Humans
Male
Models, Biological
Organic Anion Transporters
/ antagonists & inhibitors
Probenecid
/ administration & dosage
Rifampin
/ pharmacokinetics
drug-drug interaction (DDI)
furosemide
organic anion transporter (OAT)
physiologically based pharmacokinetic modeling (PBPK)
probenecid
Journal
Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521
Informations de publication
Date de publication:
25 Nov 2020
25 Nov 2020
Historique:
received:
24
08
2020
accepted:
26
10
2020
entrez:
25
11
2020
pubmed:
26
11
2020
medline:
5
8
2021
Statut:
epublish
Résumé
To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling. PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration-time curve (AUC) and peak plasma concentrations (C The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI C Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs.
Identifiants
pubmed: 33237382
doi: 10.1007/s11095-020-02964-z
pii: 10.1007/s11095-020-02964-z
pmc: PMC7688195
doi:
Substances chimiques
Organic Anion Transporters
0
Furosemide
7LXU5N7ZO5
Probenecid
PO572Z7917
Rifampin
VJT6J7R4TR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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