Cyp3a4-Mediated in vitro Metabolism and in vivo Disposition of Lorlatinib in Rats
Lorlatinib undergoes extensive CYP3A4-mediated metabolism, exhibits nonlinear PK, and shows poor oral bioavailability in rats. Significant interspecies differences between HLM and RLM emphasize the need for caution when translating preclinical findings. Coadministration with CYP3A4 modulators markedly altered systemic exposure, while effective brain penetration supports its therapeutic role in central nervous system (CNS) metastases.
Authors
- Tianjia Guan (ORCID: https://orcid.org/0000-0002-7820-2898)
- Yilei Li (ORCID: https://orcid.org/0000-0003-1410-5826)
- Cong Xie (ORCID: https://orcid.org/0000-0002-0054-9269)
- Jiayu Chen
- Ping Zheng (ORCID: https://orcid.org/0000-0003-2780-9005)
- Jin Huang (ORCID: https://orcid.org/0000-0002-0698-1693)
Institutions
- Nanfang Hospital (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- Drug Design Development and Therapy
- Published
- 2025-10-01
- DOI
- https://doi.org/10.2147/dddt.s565228
- Primary Topic
- Lung Cancer Treatments and Mutations
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Southern Medical University
- China International Medical Foundation