In Vitro Assessment of the Drug-Drug Interaction Potential of Verinurad and Its Metabolites as Substrates and Inhibitors of Metabolizing Enzymes and Drug Transporters
| Autor: | Caroline A. Lee, V. Sashi Gopaul, Constanze Hilgendorf, Tommy B. Andersson, Susanne Johansson, Anna Vildhede, Fredrik Erlandsson |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Abcg2 biology Organic anion transporter 1 CYP2B6 CYP3A4 Chemistry Pyridines Multidrug resistance-associated protein 2 Transporter Biological Transport Naphthalenes Neoplasm Proteins Pharmacokinetics biology.protein Molecular Medicine ATP Binding Cassette Transporter Subfamily G Member 2 Humans Drug Interactions Propionates Glucuronide |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 378(2) |
| ISSN: | 1521-0103 |
| Popis: | Verinurad is a selective uric acid transporter 1 (URAT1) inhibitor in development for the treatment of chronic kidney disease and heart failure. In humans, two major acyl glucuronide metabolites have been identified: direct glucuronide M1 and N-oxide glucuronide M8. Using in vitro systems recommended by regulatory agencies, we evaluated the interactions of verinurad, M1, and M8 with major drug-metabolizing enzymes and transporters and the potential for clinically relevant drug-drug interactions (DDIs). The IC50 for inhibition of CYP2C8, CYP2C9, and CYP3A4/5 for verinurad was ≥14.5 µM, and maximum free plasma concentration (Iu,max)/IC50 was |
| Databáze: | OpenAIRE |
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