Sunitinib-paracetamol sex-divergent pharmacokinetics and tissue distribution drug-drug interaction in mice

Summary 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 AUC 0→∞ , 31% and 27% lower liver and kidney AUC 0→∞ and 2.2-fold higher AUC 0→∞ in brain (all p