Cytochrome P450 3A4 Induction: Lumacaftor versus Ivacaftor Potentially Resulting in Significantly Reduced Plasma Concentration of Ivacaftor
Conclusion: All in all, present findings would suggest that lumacaftor and ivacaftor-M6 are strong inducers of CYP3A4, potentially reducing ivacaftor concentrations; ivacaftor itself induces CYP3A4 to some extent. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - August 28, 2018 Category: Drugs & Pharmacology Source Type: research
Effect of CYP2D6 Poor Metabolizer Phenotype on Stereoselective Nebivolol Pharmacokinetics
Conclusion: The decline in plasma concentration of both nebivolol isomers in PM phenotypes, especially those with MR of 220 and 244, which indicate minimal or absent CYP2D6 activity, points to alternative mechanisms for nebivolol elimination. Collectively, our results are the first to show the significant impact of CYP2D6 PM phenotype on the metabolic disposition and in vivo exposure to both nebivolol isomers. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - August 28, 2018 Category: Drugs & Pharmacology Source Type: research
Evaluation of Herb-Drug Interaction of Synacinn™ and Individual Biomarker through Cytochrome 450 Inhibition Assay
Conclusion: Curcumin was found to be an active constituent that might contribute to the inhibition of SynacinnTM against CYP2C8, CYP2C9 and CYP2C19. It can be suggested that SynacinnTM can be consumed separately from a drug known to be metabolized by all tested CYP450 enzymes. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - August 28, 2018 Category: Drugs & Pharmacology Source Type: research
LC-MS/MS Identification and Structural Characterization of Main Biodegradation Products of Nitroproston - A Novel Prostaglandin-based Pharmaceutical Compound
Conclusion: It was found that Nitroproston is rapidly hydrolyzed in rodent compared to human plasma incubations. Whereas Nitroproston is relatively stable in human plasma an enhanced hydrolytic activity was observed in whole human blood incubations. Extensive metabolism of Nitroproston in human whole blood was mainly associated with red blood cells. The observed interspecies variability highlights the need of suitable animal model selection for Nitroproston follow-up PK/PD studies. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - August 28, 2018 Category: Drugs & Pharmacology Source Type: research
In vitro Drug Metabolism Investigation of 7-Ethoxycoumarin in Human, Monkey, Dog and Rat Hepatocytes by High Resolution LC-MS/MS
Conclusion: Most of new metabolites via oxidative ring-opening and glutathionation were identified. Species differences in metabolism of 7-ethoxylcoumarin in hepatocytes were observed. The analysis of metabolites suggests that 7-ethoxylcoumarin may undergo 3,4-epoxidation responsible for formation of glutathione and its derived cysteine conjugates, carboxylic acid and its glucuronides, glucosides and sulfate. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - August 28, 2018 Category: Drugs & Pharmacology Source Type: research
Characterization of Liver- and Cancer-type-Organic Anion Transporting Polypeptide (OATP) 1B3 Messenger RNA Expression in Normal and Cancerous Human Tissues
Conclusion: Our findings are supportive of the potential role of Lt-OATP1B3 in cancer cells. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - August 28, 2018 Category: Drugs & Pharmacology Source Type: research
Cytochrome P450 1A2 Messenger RNA is a More Reliable Marker than Cytochrome P450 1A2 Activity, Phenacetin O-Deethylation, for Assessment of Induction Potential of Drug-Metabolizing Enzymes Using HepaRG Cells
Conclusion: The measurement of mRNA serves as a higher reliable indicator for the evaluation of CYP induction potential when using HepaRG cells. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - August 28, 2018 Category: Drugs & Pharmacology Source Type: research
Utility of Pooled Cryopreserved Human Enterocytes as an In vitro Model for Assessing Intestinal Clearance and Drug-Drug Interactions
Background: A recent advancement in isolation and cryopreservation has resulted in commercially available primary human enterocytes that express various drug metabolizing enzymes (DMEs) and transporters. The main objective of this study was to further evaluate the utility of pooled cryopreserved enterocytes, specifically MetMax™ cryopreserved human enterocytes (In vitro ADMET Laboratories), as an in vitro model for assessing intestinal clearance in comparison to hepatocytes. Methods: It was found that, for CYP3A4/5 substrates such as midazolam, amprenavir and loperamide, in vitro metabolic clearance is generally lower in...
Source: Drug Metabolism Letters - August 28, 2018 Category: Drugs & Pharmacology Source Type: research
Preface
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - August 28, 2018 Category: Drugs & Pharmacology Source Type: research
Meet Our Editorial Board Member
(Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - August 28, 2018 Category: Drugs & Pharmacology Source Type: research
Genotoxicity of 4-(piperazin-1-yl)-8-(trifluoromethyl)pyrido[2,3-e][1,2,4] triazolo[4,3-a]pyrazine, a Potent H4 Receptor Antagonist for the Treatment of Allergy: Evidence of Glyoxal Intermediate Involvement
Conclusion: In the present investigation, a novel method was developed to trap glyoxal, which may potentially be liberated from piperazine moiety. These findings led to modifications on the piperazine ring to mitigate the bioactivation pathways leading to mutagenicity. Subsequently, the next generation compounds with modified piperazine moiety, retained H4R inhibitory potency in vitro and were not genotoxic in the Ames mutagenicity assay. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research
Evaluation of Farnesoid X Receptor Target Gene Induction in Human Hepatocytes: Amino Acid Conjugation
Conclusion: In conclusion, there appears to be some species differences in the activation of FXR target genes. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research
Transactivation Assays that Identify Indirect and Direct Activators of Human Pregnane X Receptor (PXR, NR1I2) and Constitutive Androstane Receptor (CAR, NR1I3)
Conclusion: Cell based transactivation assays employing the full-length receptors and native promoters identify both direct and indirect activators of either or both human PXR and CAR. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research
Selective Suppression of CYP3A4 mRNA and Enzyme Activity by Epidermal Growth Factor in Plated Human Hepatocytes
Conclusion: Because of the larger effect on the basal CYP3A4 compared to the induced response, EGF as a media additive enables a higher dynamic range in a CYP3A4 induction assay, potentially expanding the range of donor hepatocytes suitable for use in induction studies. These findings also suggest that EGF may be an important regulator of CYP3A4 expression in vivo. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research
The Effects of Drug Metabolizing Enzyme Inhibitors on Hepatic Efflux and Uptake Transporters
Conclusion: ABT, pargyline, allopurinol and methimazole have no inhibitory effects on the studied ABC and SLC transporters, suggesting the inhibitors are unlikely to cause confounding inhibition of transporters when used in metabolism studies. However, SKF525A, menadione, raloxifene and piperine can inhibit the activities of ABC and/or SLC transporters. (Source: Drug Metabolism Letters)
Source: Drug Metabolism Letters - February 8, 2018 Category: Drugs & Pharmacology Source Type: research
