Effect of ketoconazole on the transport and metabolism of drugs in the human liver cell model

The effect of ketoconazole on the biotransformation of amiodarone, rosiglitazone, and cyclophosphamide was studied using the human liver cell model based on differentiated HepaRG spheroids. The concentrations of major metabolites of amiodarone and cyclophosphamide were found to decrease in the presence of ketoconazole, a cytochrome P450 3A4 inhibitor. The concentration of the major metabolite of rosiglitazone, N-desmethyl rosiglitazone, decreased upon the addition of either sulfaphenazole, a cytochrome P450 2C9 inhibitor, or ketoconazole. The rosiglitazone metabolism involves CYP2C9 and CYP2C19. This result is attributable to the inhibitory effect of ketoconazole on p-glycoprotein, which decreases N-desmethyl rosiglitazone concentration in the culture medium. The utilization of the human liver cell model and selective inhibitors of transporters and cytochrome P450 isoforms can serve for standardization of the studies of drug-drug interactions involved in drug transport and metabolism.

     

Synthesis of aromatic polyamidines on the basis of benzoic acid and diisocyanates

Russian Chemical Bulletin -     

Noninvasive biochemical monitoring of physiological stress by Fourier transform infrared saliva spectroscopy

Physical stress affects the immune system, activates the sympathetic (SNS) and parasympathetic (PNS) subsystems of autonomic nervous system (ANS), and increases the activity of the hypothalamic-pituitary-adrenal axis (HPA). The specific response of the major regulatory systems depends on the human functional state. Saliva is a unique diagnostic fluid, the composition of which immediately reflects the SNS, PNS, HPA and immune system response to stress. A new method of saliva biomarker determination by Attenuated Total Reflection Fourier-Transform Infrared (ATR FTIR) spectroscopy has been developed to monitor the exercise induced metabolic changes in saliva from male endurance athletes. The method has been tested using a group of professional athletes by analysing saliva samples collected before and after the exercise, and the saliva composition monitoring by ATR FTIR spectroscopy was shown to be suitable for real-time checking of response to stress.     

The effect of laminins on chemoresistance of colorectal cancer cells

Russian Chemical Bulletin - Earlier, the data on the ability of laminin-332 to protect liver cancer cells from apoptosis caused by doxorubicin, sorafenib, and gefitinib have been obtained. In order...