ArticleDrug metabolism and disposition: the biological fate of chemicals2019
Kinetic Modeling of Steady-State Situations in Cytochrome P450 Enzyme Reactions.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- Roles of Individual Human Cytochrome P450 Enzymes in Drug Metabolism.Pharmacological reviews · 2024Review
- Solvent isotope effects in the catalytic cycle of P450 CYP17A1: Computational modeling of the hydroxylation and lyase reactions.Journal of inorganic biochemistry · 2023Article
- Inhibition of Cytochrome P450 Enzymes by Drugs-Molecular Basis and Practical Applications.Biomolecules & therapeutics · 2022Review
- Roles of cytochrome P450 enzymes in pharmacology and toxicology: Past, present, and future.Advances in pharmacology (San Diego, Calif.) · 2022Article
Corrections and comments
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Authors and funding
1 author.
Funding
Abstract
In the course of investigations of the kinetics of individual reactions of cytochrome P450 (P450) enzymes, a number of points about the complexity of P450 enzyme kinetics have become apparent. Several of these are of particular relevance to work with P450 enzymes in the course of drug development and lead optimization, particularly with regard to estimating in vitro kinetic parameters and dealing with enzyme inhibitors. Modern simulation modeling has been applied to situations involving issues of preincubation time with moderate strength and strong inhibitors, inhibition by tightly bound ligands that have been identified in P450 enzymes, extensive substrate depletion, P450 reactions with a rate-limiting step after product formation, and the consumption of an inhibitor during a reaction by either a P450 enzyme being monitored or another one in a mixture. The results all follow from first principles, and simulations reveal the extent of their significance in various settings. The order of addition of substrate and inhibitors can change the apparent outcome (inhibition constant,
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