In vitro studies with human liver microsomes and P450 probe substrates were performed to characterize selectivity and mechanism of cytochrome P450 inhibition by nelfinavir mesylate. At therapeutic concentrations (steady-state plasma concentrations approximately 4 microM), nelfinavir was found to be a competitive inhibitor of only testosterone 6beta-hydroxylase (CYP3A4) with a Ki concentration o...

Sir, Fexofenadine is the active metabolite of the non-sedating antihistamine, terfenadine. Accumulation of terfenadine can cause prolongation of the QT interval and significant cardiac arrhythmias.1 Fexofenadine is reported to have no potential for QT interval disturbance.2 Phase II and III clinical trials in over 6000 patients showed no mean increases in mean QTc or serious cardiac arrhythmias...

We developed an in vitro high-throughput cocktail assay with nine major drug-metabolizing CYP enzymes, optimized for screening of time-dependent inhibition. The method was applied to determine the selectivity CYP2C8 inhibitors gemfibrozil 1-O-?-glucuronide and clopidogrel acyl-?-D-glucuronide. In incubations selective probe substrates pooled human liver microsomes were conducted 96-well plates ...

In the present study, the effects on intracellular calcium concentration ([Ca(2+)](i)) oscillations of the blockade of ether-a-go-go-related gene (ERG) K(+) channels and of Ca(2+) influx through store-operated channels (SOC) activated by [Ca(2+)](i) store depletion have been studied in GH(3) cells by means of a combination of single-cell fura-2 microfluorimetry and whole-cell mode of the patch-...

background: recently grapefruit juice is known to enhance the bioavailability of several clinically important drugs such as nifedipine, terfenadine, cyclosporine, ethinylestradiole, midazolam, and triazolam. cyclosporine is an immunosuppressive agent that used in transplantation for preventation of chronic rejection. grapefruit increase in cmax and auc of drug mediated by suppression of cyp3a4 ...