Identification and Characterization of the Human Cytosolic Sulfotransferases Mediating the Sulfation of Clioquinol and Iodoquinol
Conclusion: Collectively, these results provided a molecular basis underling the metabolism of clioquinol and iodoquinol through sulfation. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research
Inhibition of Procarcinogen Activating Enzyme CYP1A2 Activity and Free Radical Formation by Caffeic Acid and its Amide Analogues
Conclusion: From our results, caffeic acid and its amide analogues are in vitro inhibitors of human CYP1A2 catalytic activity and free radical formation. They may be useful to be developed as potential chemopreventive agents that block CYP1A2-mediated chemical carcinogenesis. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research
An Investigation of Sodium Fusidate and Recombinant Cytochrome P450 Enzymes Inhibition In-Vitro
Conclusion: These findings suggest that there is a potential for sodium fusidate to cause drug interactions when used with other agents that are substrates for rCYP1A2, rCYP2C9, rCYP2C19, rCYP2D6 or rCYP3A4. Understanding the basis of this potential drug interaction will assist in safer use of sodium fusidate in clinical practice. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research
Application of a “Fit for Purpose” PBPK Model to Investigate the CYP3A4 Induction Potential of Enzalutamide
Conclusion: A “fit for purpose” PBPK model of enzalutamide was successfully developed using public information that recapitulated it’s observed pharmacokinetics, CYP3A4 induction potential and the potential need for dose-adjustment of co-administered CYP3A substrates. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research
Intracellular Retention of Three Quinuclidine Derivatives in Caco-2 Permeation Experiments: Mechanisms and Impact on Estimating Permeability and Active Efflux Ratio
Conclusion: Our work reveals the different mechanisms involved in cellular retention of these quinuclidine derivatives, and more importantly, demonstrates the value of kinetic analyses with mathematical modeling in minimizing the bias in Papp estimation when assumptions for conventional calculations are violated. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - October 1, 2016 Category: Drugs & Pharmacology Source Type: research
New Screening Criteria Setting on Evaluation of Cytochrome P450 Induction Using HepaRG Cells with Multiplex Branched DNA Technologies in Early Drug Discovery
Conclusion: Our developed assay system, as well as the R10 value, is useful for evaluating the CYP induction potency of NCE in early drug discovery. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - September 30, 2016 Category: Drugs & Pharmacology Source Type: research
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(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - September 30, 2016 Category: Drugs & Pharmacology Source Type: research
The Uremic Toxin Indoxyl-3-Sulfate Induces CYP1A2 In Primary Human Hepatocytes
Conclusion: These results suggest that the uremic toxin, 3-INDS, is a potent CYP1A2 inducer and lends valuable mechanistic basis for how kidney disease can affect hepatic metabolism. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - September 29, 2016 Category: Drugs & Pharmacology Source Type: research
Formation of A Novel Purine Metabolite through CYP3A4 Bioactivation and Glutathione Conjugation
Conclusion: S-glutathionylation at C-6 position of a purine was proven unequivocally. This previously unreported mechanism constitutes a novel biotransformation for purines. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research
Elucidating the Mechanism of Tofacitinib Oxidative Decyanation
Conclusion: The proposed mechanism involved the initial oxidation by P450 at the α-carbon to the nitrile group generating an unstable cyanohydrin intermediate; followed by the loss of the nitrile group to form a new geminal diol metabolite (MX). (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research
In Vitro CYP2D Inhibitory Effect and Influence on Pharmacokinetics and Pharmacodynamic Parameters of Metoprolol Succinate by Terminalia arjuna in Rats
Conclusion: Based on our in vitro and in vivo findings and until further clinical drug interaction experiments are conducted, the co-administration of drugs, especially those primarily cleared via CYP2D catalyzed metabolism, with T. arjuna extracts should be done with caution. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research
Biotransformation of Cobicistat: Metabolic Pathways and Enzymes
Conclusion: This study provided a full map of COBI metabolism. These results can be used to manage CYP-mediated drug-drug interactions and adverse drug reactions that are associated with COBI-containing regimens in human. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research
In Vitro Study of UGT Metabolism and Permeability of Orientin and Isoorientin, Two Active flavonoid C-glycosides
C-glycosides are important flavonoids with significant pharmacological activities implicated in anticancer and antioxidative effects. However, their characteristics of metabolism and transportation have been rarely investigated. This research aimed to examine the metabolic characteristics of two active C-glycosides, namely, orientin and isoorientin, in human liver microsomes (HLMs) and rat liver microsomes (RLMs) and to confirm the specific uridine 5′-diphospho glucuronosyltransferase (UGT) isoforms involved in glucuronidation by HLMs. Furthermore, the permeability of orientin and isoorientin was also determined by using...
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research
Rate-Determining and Rate-Limiting Steps in the Clearance and Excretion of a Potent and Selective p21-Activated Kinase Inhibitor: A Case Study of Rapid Hepatic Uptake and Slow Elimination in Rat
Conclusion: Because the clearance of GNE1 is mediated through uptake transporters rather than metabolism, the extrahepatic expression of Oct1 in kidney and intestine in rat likely plays an important role in the IVIV disconnect in hepatic clearance prediction. The slow process of intestinal secretion is the rate-limiting step for in vivo clearance of GNE1. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research
Efficiency in Drug Discovery: Liver S9 Fraction Assay As a Screen for Metabolic Stability
Conclusion: In our opinion, replacing liver microsome and hepatocyte assays with S9 assay for high throughput metabolic screening purposes provides the combined benefit of comprehensive and high quality data at a reasonable expense for drug discovery programs. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - June 14, 2016 Category: Drugs & Pharmacology Source Type: research
