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Background  Avitinib is one type of the third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of non‐small cell lung cancer (NSCLC) with  EGFR  mutations. The purpose of this study was to investigate the effect of avitinib on the pharmacokinetics of osimertinib, one FDA approved third‐generation TIKI, both in vitro and in vivo.    Methods  The in vitro metabolic stability and inhibitory effect of avitinib on osimertinib were assessed with rat liver microsomes (RLM) to determine its IC 50  values. For the in vivo study, 18 Sprague‐Dawley rats were randomly divided into three groups: the avitinib multiple dose group (30 mg/kg avitinib once daily for seven days), the avitinib single dose group (PEG200 once daily for six days and a dose of 30 mg/kg avitinib in PEG200 on day 7) and the control group (equal amounts of PEG200 once daily for seven days). Next, all rats were given osimertinib at a dosage of 10 mg/kg. UPLC/MS‐MS was used for the determination of the concentration of osimertinib in plasma.    Results  In vitro analysis revealed that the IC 50  value of osimertinib in rat liver microsomes was 27.6 μM. When rats were pretreated with avitinib, the values of AUC and MRT of the osimertinib were increased, and its C max  and T max  were significantly extended, whereas the values of CLz/F were significantly decreased ( P  < 0.05).    Conclusions  Both in vitro and in vivo results demonstrated that a drug‐drug interaction between avitinib and osimertinib occurred and more attention should be paid when avitinib and osimertinib are synchronously administered in clinic.    Key points    Significant findings of the study  Osimertinib is the only market available third‐generation EGFR‐TKI and it has been reported that some drugs could have drug‐drug interactions with it.    What this study adds  For the first time, we systematically investigated the effect of avitinib, one newly developed third‐generation EGFR‐TKI, on the pharmacokinetics of osimertinib both in vitro and in vivo using a rat model.

Effects of avitinib on the pharmacokinetics of osimertinib in vitro and in vivo in rats