Drug Interactions of Vebreltinib, a Novel Type I c-Met Inhibitor, Coadministration With Rifampin or Itraconazole in Healthy Participants.

Authors

Jingcheng Chen, Jingxuan Wu, Yuqin Song, Jiangshuo Li, Linna Li, Lijun Li, Yanhong Kong, Xiaofang Wu, Hang Yin, Mengyu Hou, Bingyan Wang, Qiannan Gao, Ran Li, Le Wu, Weizhe Xue, Ruihua Dong

Published in

Clinical and translational science. Volume 19. Issue 7. Pages e70648.

Abstract

Vebreltinib is a novel, highly selective type I c-Met inhibitor developed for treating non-small cell lung cancer (NSCLC) and glioma. As in vitro studies indicate that vebreltinib is primarily metabolized via cytochrome P450 (CYP) 3A4, this study aimed to characterize the drug-drug interaction (DDI) potential of vebreltinib with strong CYP3A4 modulators. Following a preliminary single ascending dose (SAD) study to establish baseline safety and pharmacokinetics (PK) in healthy participants, a DDI study was designed to evaluate the impact of the strong CYP3A4 inducer rifampin and the strong CYP3A4 inhibitor itraconazole on vebreltinib exposure. In the CYP3A4 induction part of the DDI study, participants (n = 14) received 200 mg vebreltinib on Days 1 and 15, with rifampin (600 mg once daily) administered on Days 8-21. In the inhibition part, participants (n = 14) received 200 mg vebreltinib on Days 1 and 11. Itraconazole was administered as a loading dose (200 mg BID on Day 8) followed by maintenance dosing (200 mg QD from Days 9 to 19). PK blood samples were collected at predetermined time points. Vebreltinib plasma concentrations were assessed using a validated liquid chromatography-tandem mass spectrometry (LC-MS) method. Co-administration with rifampin reduced the AUC_0-t and AUC_0-∞of vebreltinib by ~65% and ~66%, respectively, whereas the C_max did not change significantly. In contrast, coadministration with itraconazole led to an increase in the AUC and C_max of vebreltinib by about 56% and 46%, respectively. Vebreltinib, both alone and in combination with rifampin or itraconazole, was well tolerated in healthy participants.

PMID:
42348314
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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