Prediction of trough concentration and ALK occupancy in plasma and cerebrospinal fluid using physiologically based pharmacokinetic modeling of crizotinib, alectinib, and lorlatinib.

Brain metastases occur in approximately 30% of patients with non-small-cell lung cancer (NSCLC). Therefore, the free drug concentration in cerebrospinal fluid (CSF) is strongly associated with the clinical efficacy. The present study aimed to develop physiologically based pharmacokinetic (PBPK) models that can predict the steady-state trough concentration (C) in plasma and CSF, as well as anaplastic lymphoma kinase (ALK) occupancy (AO), for three inhibitors: crizotinib (CRI), alectinib (ALE), and lorlatinib (LOR).

Integrated network pharmacology and serum metabolomics approach deciphers the anti-colon cancer mechanisms of Huangqi Guizhi Wuwu Decoction.

Huangqi Guizhi Wuwu Decoction (HGWD), as a classic Chinese herbal decoction, has been widely used in treating various diseases for hundreds of years. However, systematically elucidating its mechanisms of action remains a great challenge to the field. In this study, taking advantage of the network pharmacology approach, we discovered a potential new use of HGWD for patients with colon cancer (CC).