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Characterization of human alcohol dehydrogenase 4 and aldehyde dehydrogenase 2 as enzymes involved in the formation of 5-carboxylpirfenidone, a major metabolite of pirfenidone.
Drug Metab Dispos
January 2025
Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Japan.
Pirfenidone (PIR) is used in the treatment of idiopathic pulmonary fibrosis. After oral administration, it is metabolized by cytochrome P450 1A2 to 5-hydroxylpirfenidone (5-OH PIR) and further oxidized to 5-carboxylpirfenidone (5-COOH PIR), a major metabolite excreted in the urine (90% of the dose). This study aimed to identify enzymes that catalyze the formation of 5-COOH PIR from 5-OH PIR in the human liver.
View Article and Find Full Text PDFPhysiologically based pharmacokinetic modeling of small molecules: How much progress have we made?
Drug Metab Dispos
January 2025
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington. Electronic address:
Physiologically based pharmacokinetic (PBPK) models of small molecules have become mainstream in drug development and in academic research. The use of PBPK models is continuously expanding, with the majority of work now focusing on predictions of drug-drug interactions, drug-disease interactions, and changes in drug disposition across lifespan. Recently, publications that use PBPK modeling to predict drug disposition during pregnancy and in organ impairment have increased reflecting the advances in incorporating diverse physiologic changes into the models.
View Article and Find Full Text PDFBetulinic acid from Inonotus obliquus ameliorates T2DM by modulating short-chain fatty acids producing bacteria and amino acids metabolism in db/db mice.
J Ethnopharmacol
January 2025
National Health Commission Science and Technology Innovation Platform for Nutrition and Safety of Microbial Food, Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China. Electronic address:
Ethnopharmacological Relevance: Inonotus obliquus has also been used as a traditional folk medicine in Europe and Northeastern China to treat metabolic diseases. Betulinic acid (BA) is a major ingredient with anti-diabetic property derived from I. obliquus, however, its bioavailability is limited.
View Article and Find Full Text PDFA mitochondria-targeted nanozyme with enhanced antioxidant activity to prevent acute liver injury by remodeling mitochondria respiratory chain.
Biomaterials
January 2025
Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience and CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, PR China. Electronic address:
Developing nanomedicines with enhanced activity to scavenge reactive oxygen species (ROS) has emerged as a promising strategy for addressing ROS-associated diseases, such as drug-induced liver injury. However, designing nanozymes that not only remove ROS but also accelerate the repair of damaged liver cells remains challenging. Here, a two-pronged black phosphorus/Ceria nanozyme with mitochondria-targeting ability (TBP@CeO) is designed.
View Article and Find Full Text PDFDevelopment and optimization of raloxifene hydrochloride loaded lipid nanocapsule based hydrogel for transdermal delivery.
Ther Deliv
January 2025
Institute of Pharmaceutical Research, GLA University, Mathura, India.
Aim: Development and optimization of raloxifene hydrochloride loaded lipid nanocapsule hydrogel for transdermal delivery.
Method: A 3 Box-Behnken Design and numerical optimization was performed to obtain the optimized formulation. Subsequently, the optimized raloxifene hydrochloride loaded lipid nanocapsule was developed using phase inversion temperature and characterized for physicochemical properties.
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