Chemical formula: C₂₆H₂₇Cl₂FN₆O₃ Molecular mass: 560.151 g/mol PubChem compound: 56960363
Ensartinib is a kinase inhibitor of anaplastic lymphoma kinase (ALK) and inhibits other kinases including MET and ROS1. In vitro, ensartinib inhibited phosphorylation of ALK and its downstream signaling proteins AKT, ERK, and S6, thereby blocking ALK-mediated signaling pathways and inhibiting proliferation in cell lines harboring ALK fusions and mutations. In vivo, ensartinib showed anti-tumor activity in a mouse xenograft model of human NSCLC harboring an ALK fusion.
Ensartinib exposure-response relationships and the time course of the pharmacodynamic response have not been fully characterized.
At the approved recommended dosage, a mean increase in the QTc interval >20 ms was not observed.
Ensartinib mean (coefficient of variation [CV%]) maximum concentration (Cmax) is 292 ng/mL (60%), and the area under the concentration-time curve (AUC0–24h) is 4,920 ng·h/ml (62%) at the approved recommended dosage. Ensartinib steady state is reached within 15 days with a mean accumulation ratio of 2.7.
Ensartinib median (minimum, maximum) time to reach Cmax (Tmax) at steady state is 3 hours (2, 8 hours).
No clinically significant differences in ensartinib pharmacokinetics were observed following administration of ensartinib with a high-fat meal (total 800-1000 calories, >50% fat) compared to fasted conditions.
Ensartinib mean (CV%) apparent volume of distribution is 1,720 L (42%). Ensartinib is 91.6% bound to human plasma protein.
Ensartinib mean (standard deviation [SD]) steady-state half-life (t1/2) is 30 (20) hours.
Ensartinib is predominantly metabolized by CYP3A.
Following a single oral 200 mg dose of radiolabeled ensartinib, 91% of the radioactivity was recovered in feces (38% as unchanged) and 10% in urine (4.4% as unchanged).
No clinically significant differences in the pharmacokinetics of ensartinib were observed based on age (20 to 86 years), sex, race (Asian vs White), body weight (38 to 148 kg), mild to moderate renal impairment (eGFR 30 to 89 mL/min) and mild hepatic impairment (total bilirubin ≤ upper limit of normal (ULN) and AST > ULN or total bilirubin 1 to 1.5 x ULN and any AST).
The effect of severe renal impairment (eGFR 15 to 29 mL/min), end-stage renal disease (eGFR <15 mL/min) with or without hemodialysis, and moderate (total bilirubin >1.5 to ≤3 ULN and any AST) or severe (total bilirubin >3 times ULN and any AST) hepatic impairment on ensartinib pharmacokinetics is unknown.
Cytochrome P450 (CYP) Enzymes: Ensartinib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and does not induce CYP1A2, CYP2B6, or CYP3A.
Transporter Systems: Ensartinib is a P-gp substrate but is not a substrate of BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT1 or OCT2.
Ensartinib does not inhibit BCRP, P-gp, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2 or OCT3.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.