The oxidation and hypoglycaemic effect of sorafenib in streptozotocin-induced diabetic rats.
Administration, Oral
Animals
Area Under Curve
Blood Glucose
/ drug effects
Chromatography, High Pressure Liquid
Diabetes Mellitus, Experimental
/ drug therapy
Hypoglycemic Agents
/ administration & dosage
Male
Oxidation-Reduction
Protein Kinase Inhibitors
/ administration & dosage
Rats
Rats, Wistar
Sorafenib
/ administration & dosage
Streptozocin
Metabolism
Sorafenib
Sorafenib-associated hypoglycaemia
Streptozotocin-induced diabetes
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
07
05
2019
accepted:
25
08
2019
revised:
11
07
2019
entrez:
5
2
2020
pubmed:
6
2
2020
medline:
30
10
2020
Statut:
ppublish
Résumé
Diabetes reduces the activity of CYP3A4 and may increase the exposure for the drugs metabolized by the isoenzyme. Sorafenib is a multi-targeted tyrosine kinase inhibitor (TKI), used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. The TKI undergoes CYP3A4-dependent oxidative transformation, which may be influenced by hyperglycaemia. The aim of the study was to compare the oxidation for sorafenib between healthy and streptozotocin-induced diabetic rats. Additionally, the effect of sorafenib on glucose levels was investigated. The rats were assigned to the groups: streptozotocin-induced diabetic (DG, n = 8) or healthy (HG, n = 8). The rats received sorafenib orally as a single dose of 100 mg/kg. The plasma concentrations of sorafenib and its metabolite N-oxide were measured with the validated high-performance liquid chromatography with ultraviolet detection. The difference between groups in C The findings of the study provide evidence that diabetes significantly influence on the exposition for sorafenib and its metabolite, but similar ratios N-oxide/sorafenib for AUC and C
Sections du résumé
BACKGROUND
BACKGROUND
Diabetes reduces the activity of CYP3A4 and may increase the exposure for the drugs metabolized by the isoenzyme. Sorafenib is a multi-targeted tyrosine kinase inhibitor (TKI), used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. The TKI undergoes CYP3A4-dependent oxidative transformation, which may be influenced by hyperglycaemia. The aim of the study was to compare the oxidation for sorafenib between healthy and streptozotocin-induced diabetic rats. Additionally, the effect of sorafenib on glucose levels was investigated.
METHODS
METHODS
The rats were assigned to the groups: streptozotocin-induced diabetic (DG, n = 8) or healthy (HG, n = 8). The rats received sorafenib orally as a single dose of 100 mg/kg. The plasma concentrations of sorafenib and its metabolite N-oxide were measured with the validated high-performance liquid chromatography with ultraviolet detection.
RESULTS
RESULTS
The difference between groups in C
CONCLUSION
CONCLUSIONS
The findings of the study provide evidence that diabetes significantly influence on the exposition for sorafenib and its metabolite, but similar ratios N-oxide/sorafenib for AUC and C
Identifiants
pubmed: 32016844
doi: 10.1007/s43440-019-00021-0
pii: 10.1007/s43440-019-00021-0
pmc: PMC8187206
doi:
Substances chimiques
Blood Glucose
0
Hypoglycemic Agents
0
Protein Kinase Inhibitors
0
Streptozocin
5W494URQ81
Sorafenib
9ZOQ3TZI87
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
254-259Commentaires et corrections
Type : ErratumIn
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