Effect of Cyclosporin A and Impact of Dose Staggering on OATP1B1/1B3 Endogenous Substrates and Drug Probes for Assessing Clinical Drug Interactions.
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
03
08
2021
accepted:
28
02
2022
pubmed:
17
3
2022
medline:
21
5
2022
entrez:
16
3
2022
Statut:
ppublish
Résumé
This study was designed to assess the quantitative performance of endogenous biomarkers for organic anion transporting polypeptide (OATP) 1B1/1B3-mediated drug-drug interactions (DDIs). Ten healthy volunteers orally received OATP1B1/1B3 probe cocktail (0.2 mg pitavastatin, 1 mg rosuvastatin, and 2 mg valsartan) and an oral dose of cyclosporin A (CysA, 20 mg and 75 mg) separated by a 1-hour interval (20 mg (-1 hour), and 75 mg (-1 hour)). CysA 75 mg was also given with a 3-hour interval (75 mg (-3 hours)) to examine the persistence of OATP1B1/1B3 inhibition. The area under the plasma concentration-time curve ratios (AUCRs) were 1.63, 3.46, and 2.38 (pitavastatin), 1.39, 2.16, and 1.81 (rosuvastatin), and 1.42, 1.77, and 1.85 (valsartan), at 20 mg, 75 mg (-1 hour) and 75 mg (-3 hours) of CysA, respectively. CysA effect on OATP1B1/1B3 was unlikely to persist at the dose examined. Among 26 putative OATP1B1/1B3 biomarkers evaluated, AUCR and maximum concentration ratio (C
Identifiants
pubmed: 35292967
doi: 10.1002/cpt.2584
pmc: PMC9325410
doi:
Substances chimiques
Liver-Specific Organic Anion Transporter 1
0
Organic Anion Transporters
0
Solute Carrier Organic Anion Transporter Family Member 1B3
0
Valsartan
80M03YXJ7I
Cyclosporine
83HN0GTJ6D
Rosuvastatin Calcium
83MVU38M7Q
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1315-1323Informations de copyright
© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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