Progress in Epigenetic Modification Regulating Drug Transporters in the Hypoxic Environment.

Drug transporters are critical factors influencing the pharmacokinetics of drugs under hypoxic conditions. Studies have shown significant changes in drug transporter levels in the hypoxic environment. In addition to being regulated by HIF-1, nuclear receptors, and inflammatory factors, hypoxia can also regulate transporters through epigenetic modifications, thereby affecting drug absorption, distribution, metabolism, and excretion.

Effect of High Altitude Environment on Pharmacokinetic and Pharmacodynamic of Warfarin in Rats.

Background: High altitude environment affects the pharmacokinetic (PK) parameters of drugs and the PK parameters are an important theoretical basis for guiding the rational clinical use of drugs. Warfarin is an oral anticoagulant of the coumarin class commonly used in clinical practice, but it has a narrow therapeutic window and wide individual variation. However, the effect of high altitude environment on PK and pharmacodynamic (PD) of warfarin is unclear.

Effects of hypoxia on the expression and function of P-gp in Caco-2 cells.

Objectives: Hypoxia can alter the oral bioavailability of drugs, including various substrates (drugs) of P-glycoprotein (P-gp), suggesting that hypoxia may affect the function of P-gp in intestinal epithelial cells. Currently, Caco-2 monolayer model is the classic model for studying the function of intestinal epithelial P-gp. This study combines the Caco-2 monolayer model with hypoxia to investigate the effects of hypoxia on the expression and function of P-gp in Caco-2 cells, which helps to elucidate the mechanism of changes in drug transport on intestinal epithelial cells in high-altitude hypoxia environment.

Effects of high-altitude environment on pharmacokinetic parameters of gliquidone in rats.

Objective: To investigate the effect of high-altitude hypoxia on the pharmacokinetics parameters of gliquidone.

Methods: Twelve healthy male Wistar rats were randomly divided into plain group and high-altitude group with 6 rats in each group. Blood samples were collected after intragastric administration of gliquidone (6.

Research Progress of Epigenetic Modification on the Regulation of Transporters Under Hypoxia.

Epigenetic modification refers to the heritable changes caused by chromosomal changes without changing the DNA sequence. Epigenetics runs through the entire growth and differentiation process of the body, which causes varied diseases. Hypoxia is a physiological astate of lowered partial oxygen partial pressure that affects cell and tissue function.

Development of tartaric acid derived chiral guanidines and their application to catalytic enantioselective α-hydroxylation of β-dicarbonyl compounds.

A novel library of chiral guanidines featuring a tartaric acid skeleton was developed from diethyl l-tartrate. These guanidines are easily accessed with tunable steric and electronic properties. The utilities of the guanidines were highlighted by their ability to catalyze the α-hydroxylation of β-ketoesters and β-diketones with remarkable efficiency and excellent enantioselectivity.