Mengxin Huang
((1) School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China (2)Drug Clinical Trial Institution, The First Affiliated Hospital of Xiamen University, Xiamen, China)
Background:
C019199 is a novel oral CSF-1R inhibitor for tenosynovial giant cell tumor and other solid tumors. However, the inhibitory and inducible effects of C019199 on the activity of cytochrome P450 (CYP450) is unclear.
Method:
Human liver microsomes and primary hepatocytes were used as in vitro models.
Results:
C019199 was rapidly metabolized with poor stability across species liver microsomes. In hepatocytes, it showed faster metabolism in beagle dogs and moderate stability in humans and rats. C019199 at 0.102 and 1.02 µM showed no induction on CYP1A2, CYP2B6 and CYP3A4, while 10.22 µM caused partial cell death. It strongly inhibited CYP2C9, moderately inhibited CYP1A2, CYP2B6, CYP2C8, CYP2C19 and CYP2D6, but had no inhibition on CYP3A4.
Conclusion:
C019199 may cause CYP?mediated drug?drug interactions, which deserves clinical attention.
Acknowledgments:
Supported by the Science and Technology Plan Guiding Project of Xiamen (3502Z20244ZD1042).
Mengxin Huang
((1) School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China (2)Drug Clinical Trial Institution, The First Affiliated Hospital of Xiamen University, Xiamen, China)
Wenrui Zhang
((1) School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China (2)Drug Clinical Trial Institution, The First Affiliated Hospital of Xiamen University, Xiamen, China)
Xi Luo
(Drug Clinical Trial Institution, The First Affiliated Hospital of Xiamen University, Xiamen, China)
Xiaoqing Wen
(Drug Clinical Trial Institution, The First Affiliated Hospital of Xiamen University, Xiamen, China)
Yueyuan Huang
(Drug Clinical Trial Institution, The First Affiliated Hospital of Xiamen University, Xiamen, China)
Ziyi Zhou
((1) School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China (2)Drug Clinical Trial Institution, The First Affiliated Hospital of Xiamen University, Xiamen, China)
