In vivo assessment of potential for UGT-inhibition-based drug-drug interaction between sorafenib and tapentadol.
Adrenergic Uptake Inhibitors
/ pharmacology
Animals
Antineoplastic Agents
/ blood
Area Under Curve
Chromatography, High Pressure Liquid
Drug Interactions
Glucuronides
/ metabolism
Glucuronosyltransferase
/ antagonists & inhibitors
Male
Rats
Rats, Wistar
Reproducibility of Results
Sorafenib
/ blood
Spectrophotometry, Ultraviolet
Tandem Mass Spectrometry
Tapentadol
/ pharmacology
Drug-drug interaction
Pharmacokinetics
Sorafenib
Sorafenib N-oxide
Tapentadol
Tapentadol glucuronide
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
11
05
2020
revised:
07
07
2020
accepted:
11
07
2020
pubmed:
28
7
2020
medline:
23
3
2021
entrez:
27
7
2020
Statut:
ppublish
Résumé
Sorafenib (SR) is one of the most potent UGT (1A1, 1A9) inhibitors (in in vitro tests). The inhibition of UGT1A1 may cause hyperbilirubinaemia, whereas the inhibition of UGT1A9 and 1A1 may result in drug-drug interactions (DDIs). Tapentadol (TAP) is a synthetic μ-opioid agonist and is used to treat moderate to severe acute pain. Tapentadol is highly glucuronidated by the UGT1A9 and UGT2B7 isoenzymes. The aim of the study was to assess the DDI between SR and TAP. Wistar rats were divided into three groups, with eight animals in each. The rats were orally treated with SR (100 mg/kg) or TAP (4.64 mg/kg) or in combination with 100 mg/kg SOR and 4.64 TAP mg/kg. The concentrations of SR and sorafenib N-oxide, TAP and tapentadol glucuronide were respectively measured by means of high-performance liquid chromatography (HPLC) with ultraviolet detection and by means of ultra-performance liquid chromatography-tandem mass spectrometry. The co-administration of TAP with SR caused TAP maximum plasma concentration (C
Identifiants
pubmed: 32712531
pii: S0753-3322(20)30723-X
doi: 10.1016/j.biopha.2020.110530
pii:
doi:
Substances chimiques
Adrenergic Uptake Inhibitors
0
Antineoplastic Agents
0
Glucuronides
0
Ugt1a1 protein, rat
0
Sorafenib
9ZOQ3TZI87
Glucuronosyltransferase
EC 2.4.1.17
Tapentadol
H8A007M585
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
110530Informations de copyright
Copyright © 2020. Published by Elsevier Masson SAS.