Sunitinib-paracetamol sex-divergent pharmacokinetics and tissue distribution drug-drug interaction in mice.
Invest New Drugs
; 35(2): 145-157, 2017 04.
Article
in En
| MEDLINE
| ID: mdl-28070719
ABSTRACT
The sex-divergent pharmacokinetics and interaction of tyrosine kinase inhibitor sunitinib with paracetamol was evaluated in male and female mice. Mice (control groups) were administered 60 mg/kg PO sunitinib alone or with 200 mg/kg PO paracetamol (study groups). Sunitinib concentration in plasma, brain, kidney and liver were determined and non-compartmental pharmacokinetic analysis performed. Female control mice showed 36% higher plasma sunitinib AUC0â∞, 31% and 27% lower liver and kidney AUC0â∞ and 2.2-fold higher AUC0â∞ in brain (all p < 0.001) and had lower liver- and kidney-to-plasma AUC0â∞ ratios (p < 0.001) than male control mice. Paracetamol decreased 29% plasma AUC0â∞ (p < 0.05) in male mice and remained unchanged in female mice. In male and female mice, it decreased liver (15%, 9%), kidney (15%, 20%) and brain (47%, 50%) AUC0â∞ (p < 0.001) respectively owing to 52% brain uptake efficiency reduction in female mice (p < 0.01). Sunitinib displayed sex-divergent pharmacokinetics, tissue distribution and DDI with potential clinical translatability for the treatment of brain tumor and RCC patients.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrroles
/
Analgesics, Non-Narcotic
/
Angiogenesis Inhibitors
/
Protein Kinase Inhibitors
/
Indoles
/
Acetaminophen
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Invest New Drugs
Year:
2017
Document type:
Article
Affiliation country:
Malaysia