The Influence of a Rat Model of Depression and Gastric Ulcer on the Pharmacokinetics of Encorafenib

ABSTRACT Encorafenib is used to treat melanoma and colorectal tumors. Depression and gastric ulcer conditions can impact various physiological processes, including drug metabolism and pharmacokinetics. This study investigated the effect of a rat model of depression and gastric ulcers on the pharmacokinetics (PK) of encorafenib using the developed LC‐QqQ‐MS method. The chronic unpredictable mild stress (CUMS) model of depression and the indomethacin‐induced gastric ulcer model were utilized to investigate the effect of depression and gastric ulcers on the pharmacokinetics of orally administered encorafenib. The focus was on parameters such as maximum plasma concentration ( C max ), elimination half‐life ( t 1/2 ), mean residence time (MRT), volume of distribution (V d ), area under the curve (AUC), and apparent clearance (CL/F). Rats with depression exhibited a significant increase in maximum plasma concentration ( C max ). In contrast, depression led to decreased t 1/2 and MRT, implying alterations in the drug's absorption and clearance. On the one hand, rats with gastric ulcers displayed a significant decrease in C max , coupled with an extended time to reach maximum plasma concentration ( T max ), prolonged t 1/2 , MRT, and increased volume of distribution (Vd) of encorafenib. This preclinical study demonstrates that depression and gastric ulcers significantly impact the pharmacokinetics of encorafenib. These findings emphasize the importance of considering these disease conditions when designing encorafenib dosing regimens for optimal therapeutic outcomes in cancer patients.