Primary human hepatocytes in culture are commonly used to evaluate cytochrome P450 (P450) induction via an enzyme activity endpoint. However, other processes can confound data interpretation. To this end, the impact of time-dependent P450 inhibition in this system was evaluated. Using a substrate-cassette approach, P450 activities were determined after incubation with the prototypic inhibitors ...

Critically ill patients generally are older, frequently have organ failure, and commonly receive multiple medications, all of which make them susceptible to adverse effects of drugs. Drug interactions are a common adverse effect, and many are predictable based on understanding the mechanisms that underlie drug interactions. This article identifies commonly used medications in critically ill pat...

This article is a report on a symposium held at the March 1997 meeting of the American Society for Pharmacology and Experimental Therapeutics in San Diego. Current developments in the heterologous expression of cytochrome P450, NADPH-cytochrome P450 reductase, glutathione transferase, and UDP-glucuronosyltransferase enzymes are described. Systems include bacteria, insect cells, and transient an...

Of the microsomal P450 cytochromes, the ethanol-inducible isoform, P450 2E1, is believed to be predominant in leading to oxidative damage, including the generation of radical species that contribute to lipid peroxidation, and in the reductive beta-scission of lipid hydroperoxides to give hydrocarbons and aldehydes. In the present study, the sensitivity of a series of P450s to trans-4-hydroxy-2-...

BACKGROUND AND OBJECTIVE Activity of human cytochrome P450 enzymes (CYPs) shows high inter-and intra-individual variability, which is determined by genetic and non-genetic factors. Using a combination of CYP-specific probe drugs, phenotyping cocktails allow simultaneous assessment of the activity of different CYP isoforms. The objective of this study was to characterize the phenotyping metrics ...

The treatment of cancer depends on the activity cytochrome P450 enzyme family, which is essentially carried out by CYP3A4 and CYP3A5 enzymes. aim our study was to investigate whether polymorphism could contribute protein their influence response cells treatment. variability cDNA profiles between cell lines parental HT-29 resistant HT-29-OxR adenocarcinoma detected using denaturing gradient gel ...

Cytochrome P450 oxidoreductase (POR) is known as the sole electron donor in the metabolism of drugs by cytochrome P450 (CYP) enzymes in human. However, little is known about the effect of polymorphic variants of POR on drug metabolic activities of CYP3A4 and CYP2B6. In order to better understand the mechanism of the activity of CYPs affected by polymorphic variants of POR, six full-length mutan...

Artemisinin drugs have become the first-line antimalarials in areas of multidrug resistance. However, monotherapy with artemisinin drugs results in comparatively high recrudescence rates. Autoinduction of cytochrome P450 (P450)-mediated metabolism, resulting in reduced exposure, has been supposed to be the underlying mechanism. To better understand the autoinduction and metabolic drug-drug inte...

BACKGROUND The juvenile hormone mimic, pyriproxyfen is a suppressor of insect embryogenesis and development, and is effective at controlling pests such as the greenhouse whitefly Trialeurodes vaporariorum (Westwood) which are resistant to other chemical classes of insecticides. Although there are reports of insects evolving resistance to pyriproxyfen, the underlying resistance mechanism(s) are ...

Flavone analogs are natural compounds of the flavonoid class that have a wide range biological activities. The present study aimed to predict, with aid in silico methodologies, oral bioavailability and pharmacokinetic toxicological analyzes for three flavone analogues (apigenin, chrysin luteonlin). revealed good availability, favorable parameters. Virtual Screening performed predict all did not...