Lars Weidolf

TL;DR: In vitro studies suggest that lansoprazoles and pantoprazole are the most potent in vitro inhibitors of CYP2C19 and CYP3A4, respectively.

TL;DR: The results of this study show that both CYP2C19 and CYP3A4 exhibit a stereoselective metabolism of omeprazole, with predictions of the CL(int) using data from cDNA-expressed enzymes suggest that CYP 2C19 is responsible for 40 and 87% of the total CL (int) of S- and R-omeprazole in human liver microsomes.

TL;DR: Patients with a severe deficit in their liver function had a lower rate of metabolism, as would be expected, whereas those with mild to moderate liver disease did not exhibit any alteration in the pharmacokinetics.

TL;DR: An in vitro approach is evaluated, which explored both cellular effects and covalent binding (CVB) to assess IADR risks for drug candidates using 36 drugs which caused different patterns and severities of IADRs in humans, and it is proposed that this integrated approach has the potential to enable selection of drug candidates with reduced propensity to cause IADS in humans.

TL;DR: The activities of Isotope Chemistry at AstraZeneca is described and a brief overview of different commonly used approaches for the preparation of (14)C- and (3)H-labeled drug candidates are presented with in-house examples where relevant.