Sex Differences in the Pharmacokinetics of Icotinib, a Novel EGFR-TKI, in Rats

To determine the sex differences in the pharmacokinetics of icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, we examined the plasma levels of icotinib in male and female rats treated with a single oral administration of icotinib (35 mg/kg) by a rapid, sensitive and accurate UPLC-UV method. Our study revealed that the plasma levels of icotinib in the female rats had significantly increased compared to male rats. The AUC(0-infinity) C-max and T-max of icotinib in female rats group were 4.59-, 1.98- and 222 -fold higher than those in male rats group (P < 0.01, respectively), and the CL/F and t1/2 were 4.72- and 1.43-fold lower than those in male rats group (both P < 0.01). These results demonstrate the existence of marked gender differences for icotinib in rats. Therefore, icotinib administration should be carefully considered in women.