Fig. 5

Pharmacokinetics and Pharmacodynamics of adagrasib and abemaciclib in xenograft brain metastasis mouse models. The treatment protocol involves administering adagrasib at 75 mg/kg BID, abemaciclib at 50 mg/kg daily, or their combination via oral gavage to n/n mice with intracranially injected H2122 (150,000 cells) or SW1573 (200,000 cells) cell line xenografts (n = 3/group, n = 4/combination group). The treatment spans a total of 3 days, and blood and brain collection were performed 3 h after the last dose. For the vehicle group, sample collection was made at 1 h after the last dose. Pharmacokinetic samples were collected from the plasma and right hemisphere of the brain, while pharmacodynamic samples were collected from the right hemisphere. A, Pharmacokinetics data plots illustrate drug concentration in plasma and brain samples of H2122 xenograft models, comparing single agents with combination treatment. B, Pharmacokinetics data plots illustrate drug concentration in plasma and brain samples of SW1573 xenograft models, comparing single agents with combination treatment. C, Pharmacodynamics, IHC, and quantitative data of cellular markers, p-ERK, p-Rb, Ki67, and C-Cas3 (Cleaved caspase 3), along with data plots illustrating the percentage of positive cells (%) between the groups in brain samples of the SW1573 xenograft-bearing mice used in the pharmacokinetic study