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Population Pharmacokinetics of Sotorasib in Healthy Subjects and Advanced Solid Tumor Patients Harboring a KRAS Mutation from Phase 1 and Phase 2 Studies.
AAPS J
January 2025
Clinical Pharmacology Modeling and Simulation, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320-0777, USA.
Sotorasib is a novel KRAS inhibitor that has shown robust efficacy, safety, and tolerability in patients with KRAS mutation. The objectives of the population pharmacokinetic (PK) analysis were to characterize sotorasib population PK in healthy subjects and patients with advanced solid tumors with KRAS mutation from 6 clinical studies, evaluate the effects of intrinsic and extrinsic factors on PK parameters, and perform simulations to further assess the impact of identified covariates on sotorasib exposures. A two-compartment disposition model with three transit compartments for absorption and time-dependent clearance and bioavailability well described sotorasib PK.
View Article and Find Full Text PDFRatio of Skeletal Muscle Mass to Visceral Fat Area Is a Useful Marker for Assessing Left Ventricular Diastolic Dysfunction among Koreans with Preserved Ejection Fraction: An Analysis of the Random Forest Model.
J Obes Metab Syndr
January 2025
Division of Cardiology, Department of Internal Medicine, Chungnam National University Sejong Hospital, Chungnam National University College of Medicine, Sejong, Korea.
Background: Although the presence of both obesity and reduced muscle mass presents a dual metabolic burden and additively has a negative effect on a variety of cardiometabolic parameters, data regarding the associations between their combined effects and left ventricular diastolic function are limited. This study investigated the association between the ratio of skeletal muscle mass to visceral fat area (SVR) and left ventricular diastolic dysfunction (LVDD) in patients with preserved ejection fraction using random forest machine learning.
Methods: In total, 1,070 participants with preserved left ventricular ejection fractions who underwent comprehensive health examinations, including transthoracic echocardiography and bioimpedance body composition analysis, were enrolled.
Factors Associated with High Intrathoracic Pressure in Obese Patients Undergoing Right Heart Catheterization.
Chest
January 2025
Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH, United States. Electronic address:
Role of AIM2 and cGAS-STING signaling in high fat high carbohydrate diet-induced gut dysbiosis associated neurodegeneration.
Life Sci
January 2025
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research, Chunilal Bhawan, 168, Maniktala Main Rd, Kolkata, West Bengal 700054, India. Electronic address:
Aims: Gut dysbiosis modulates CNS complications and cognitive decline through the gut-brain axis. The study aims to investigate the molecular mechanisms involved in gut dysbiosis-associated cognitive changes and the potential effects of probiotics in high fat-high carbohydrate diet-induced gut dysbiosis-associated neurodegeneration.
Materials And Methods: We used high fat, high-carbohydrate diet (HFHCD) and high-fat diet (HFD) to induce gut dysbiosis-associated neurodegeneration in C57BL/6 mice.
Secondary bile acid derivatives are contributors to the fecal bile acid pool and associated with bile acid modulating nutrients.
J Nutr
January 2025
Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, IL, USA; University of Illinois Cancer Center, Chicago, Illinois, USA. Electronic address:
Objective: Accumulation of hydrophobic bile acids is linked with cancer development. However, derivatives of deoxycholic acid (DCA) and lithocholic acid (LCA) produced via bacterial metabolism may mitigate the proinflammatory and cytotoxic effects of hydrophobic bile acids. The impact of diet on secondary bile acid (BA) derivative production has not been determined.
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