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Clinical Evaluation of Drug-Drug Interactions with Obeldesivir, an Orally Administered Antiviral Agent.
Clin Pharmacol Ther
January 2025
Gilead Sciences, Inc., Foster City, California, USA.
Obeldesivir is an oral nucleoside analog prodrug inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase and other viral polymerases. Here, two Phase I studies evaluated potential drug-drug interactions between obeldesivir and substrates or inhibitors of cytochrome P450 and drug transporters in healthy participants. When obeldesivir was tested as a precipitant, pharmacokinetic parameter point estimates for midazolam (CYP3A4 inhibition/induction), caffeine (CYP1A2 inhibition), and metformin (organic cation transporter 1 inhibition) exposures were within 80-125% no-effect bounds representing the interval within which a systemic exposure change does not warrant clinical action based on EMA/FDA guidance.
View Article and Find Full Text PDFLow-Dose Caffeine Supplementation Is a Valuable Strategy for Increasing Time to Exhaustion, Explosive Power, and Reducing Muscle Soreness in Professional Male Kickboxers.
Curr Dev Nutr
January 2025
Department of Exercise Physiology, University of Isfahan, Isfahan, Iran.
Background: Caffeine is a well-established ergogenic aid that enhances physical performance and recovery. However, its dose-dependent effects on key performance metrics in combat sports like kickboxing remain insufficiently explored.
Objective: This study aimed to evaluate the effects of varied doses of acute caffeine supplementation on performance indices and perceived muscle pain in kickboxing athletes.
An mTOR inhibitor discovery system using drug-sensitized yeast.
Geroscience
January 2025
Department of Biomedical Sciences, Western University of Health Sciences, Lebanon, OR, 97355, USA.
Inhibition of the target of rapamycin (TOR/mTOR) protein kinase by the drug rapamycin extends lifespan and health span across diverse species. However, rapamycin has potential off-target and side effects that warrant the discovery of additional TOR inhibitors. TOR was initially discovered in Saccharomyces cerevisiae (yeast) which contains two TOR paralogs, TOR1 and TOR2.
View Article and Find Full Text PDFThe effect of dietary supplements on core temperature and sweating responses in hot environmental conditions: a meta-analysis and meta-regression.
Am J Physiol Regul Integr Comp Physiol
January 2025
A-STEM Centre, Faculty of Science and Engineering, Swansea University, Swansea, UK.
Dietary supplements are widely used among individuals exposed to hot environments, but whether their consumption confers any thermoregulatory effect is unclear. Therefore, we systematically evaluated the effect of dietary supplementation on key aspects of thermoregulation (core temperature [T] and sweating responses) in the heat. Three databases were searched in April 2024.
View Article and Find Full Text PDFCloning and functional characterization of the caffeine oxidase gene CsCDH from Camellia sinensis.
Int J Biol Macromol
January 2025
Key Laboratory of Tea Science, Ministry of Education, Hunan Agricultural University, Changsha 410128, Hunan, China; National Engineering Research Center for Utilization of Functional Ingredients from Plants, Hunan Agricultural University, Changsha 410128, Hunan, China; Collaborative Innovation Center for Utilization of Functional Ingredients from Plants, Ministry of Education, Hunan Agricultural University, Changsha 410128, Hunan, China. Electronic address:
Theacrine, a purine alkaloid with pharmacological effects such as calming and anti-depressive activities, is biosynthesized through a key rate-limiting enzyme, caffeine oxidase. Despite its importance, the caffeine oxidase gene (CsCDH) in Camellia sinensis has not been cloned to date. We successfully isolated the full-length CsCDH cDNA, which contains a 501-bp open reading frame (ORF) encoding a 166-amino-acid protein with a calculated molecular weight of 18.
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