Effects of Voriconazole on the Pharmacokinetics of Vonoprazan in Rats.
cytochrome P450
drug–drug interaction
pharmacokinetic
proton pump inhibitor
Journal
Drug design, development and therapy
ISSN: 1177-8881
Titre abrégé: Drug Des Devel Ther
Pays: New Zealand
ID NLM: 101475745
Informations de publication
Date de publication:
2020
2020
Historique:
received:
25
03
2020
accepted:
19
05
2020
entrez:
26
6
2020
pubmed:
26
6
2020
medline:
31
3
2021
Statut:
epublish
Résumé
The purpose of this study was to examine the effects of voriconazole on the pharmacokinetics of vonoprazan. Fifteen Sprague-Dawley rats were randomly divided into three groups: five rats in each group, including control group, single-dose group (a single dose of 30 mg/kg of voriconazole), and multiple-dose group (multiple doses of 30 mg/(kg•day) per dose of voriconazole). Each group of rats was given an oral dose of 10 mg/kg vonoprazan 30 min after the administration of voriconazole or vehicle. After the oral administration of vonoprazan, 50 µL of blood was collected into 1.5-mL heparinized tubes via the caudal vein. The concentration of vonoprazan in plasma was quantified by ultra-performance liquid chromatography/tandem mass spectrometry. Both in vitro effects of voriconazole on vonoprazan and the mechanism of the observed inhibition were studied in rat liver microsomes. When orally administered, voriconazole increased the area under the plasma concentration-time curve (AUC), prolonged the elimination half-life (t Our findings provide the evidence of drug-drug interactions between voriconazole and vonoprazan that could occur with pre-administration of voriconazole. Thus, clinicians should pay attention to the resulting changes in pharmacokinetic parameters and accordingly, adjust the dose of vonoprazan in clinical settings.
Identifiants
pubmed: 32581516
doi: 10.2147/DDDT.S255427
pii: 255427
pmc: PMC7280087
doi:
Substances chimiques
1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
0
Pyrroles
0
Sulfonamides
0
Voriconazole
JFU09I87TR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2199-2206Informations de copyright
© 2020 Shen et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
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