2,561 results match your criteria cyp activities

Potential Cytochrome P450-mediated pharmacokinetic interactions between herbs, food, and dietary supplements and cancer treatments.

Crit Rev Oncol Hematol 2021 Apr 27:103342. Epub 2021 Apr 27.

Sorbonne Université, INSERM CIC Paris-Est, AP-HP, ICAN, Pitié-Salpêtrière Hospital, Department of Pharmacology, F-75013, Paris, France.

Herbs, food and dietary supplements (HFDS), can interact significantly with anticancer drug treatments via cytochrome p450 isoforms (CYP) CYP3A4, CYP2D6, CYP1A2, and CYP2C8. The objective of this review was to assess the influence of HFDS compounds on these cytochromes. Interactions with CYP activities were searched for 189 herbs and food products, 72 dietary supplements in Web of Knowledge® databases. Read More

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An Efficient Method for the Differentiation of Human iPSC-Derived Endoderm toward Enterocytes and Hepatocytes.

Cells 2021 Apr 6;10(4). Epub 2021 Apr 6.

Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.

The endoderm, differentiated from human induced pluripotent stem cells (iPSCs), can differentiate into the small intestine and liver, which are vital for drug absorption and metabolism. The development of human iPSC-derived enterocytes (HiEnts) and hepatocytes (HiHeps) has been reported. However, pharmacokinetic function-deficiency of these cells remains to be elucidated. Read More

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Conversion of five proluciferin esters by human cytochrome P450 enzymes.

Biotechnol J 2021 Apr 28:e2100007. Epub 2021 Apr 28.

School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin, 300072, China.

Background: Probe substrates are an important tool for activity monitoring of human drug metabolizing enzymes such as cytochromes P450 (CYPs).

Brief Methods: In the present study we have tested human CYPs for metabolization of five proluciferin ester substrates which had previously only been known to be hydroxylated by CYP26A1.

Major Results: It was found that these substrates were converted by another 21 human CYPs, which belong to the CYP families 1 to 4, 7, and 26. Read More

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A high-throughput cell-based gaussia luciferase reporter assay for measurement of CYP1A1, CYP2B6, and CYP3A4 induction.

Xenobiotica 2021 May 3:1-12. Epub 2021 May 3.

Institute of Radiation Medicine Academy of Military Medical Sciences, Beijing, China.

The induction of cytochrome P450s can result in reduced drug efficacy and lead to potential drug-drug interactions. The xenoreceptors-aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR)-play key roles in CYP induction by xenobiotics. In order to be able to rapidly screen for the induction of three enzymes (CYP1A1, CYP2B6, and CYP3A4), we generated a stable AhR-responsive HepG2 cell line, a stable CAR-responsive HepG2 cell line, and a stable PXR-responsive HepG2 cell line. Read More

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Identification, methylation profiling, and expression analysis of stress-responsive cytochrome P450 genes in rice under abiotic and phytohormones stresses.

GM Crops Food 2021 Apr 20:1-13. Epub 2021 Apr 20.

College of Economics and Management, Kunming University, Kunming China.

The cytochrome P450 (CYP) is a large and complex eukaryotic gene superfamily with enzymatic activities involved in several physiological and regulatory processes. As an objective, an genome-wide DNA methylation (5mC) analysis was performed in rice ( cv. Zhonghua11), and the epigenetic role of CYPs in two abiotic stresses was observed. Read More

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The inhibition of CYP1A2, CYP2C9, and CYP2D6 by pterostilbene in human liver microsomes.

Pharmazie 2021 Apr;76(4):155-158

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh.

This study used human liver microsomes to assess pterostilbene's effect on the metabolic activity of cytochrome P450 (CYP) 1A2, CYP2C9, and CYP2D6. The metabolism of their substrates (phenacetin, tolbutamide, and dextromethorphan) was assayed by quantifying their relevant metabolites by HPLC. The IC value was used to express the strength of inhibition, and the value of a volume per dose index (VDI) was used to indicate the metabolic ability of the enzyme. Read More

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Dimethyl Sulfoxide: Morphological, Histological, and Molecular View on Developing Chicken Liver.

Toxics 2021 Mar 12;9(3). Epub 2021 Mar 12.

Department of Morphological Disciplines, University of Veterinary Medicine and Pharmacy in Kosice, Komenskeho 73, 041 81 Kosice, Slovakia.

Dimethyl sulfoxide (DMSO) is widely used as a solvent for small hydrophobic drug molecules. However, the safe volume allowing to avoid its embryotoxic effect has been poorly studied. In this study, we documented the effects of dimethyl sulfoxide (DMSO) in the developing chicken embryo at morphological, histological, and molecular levels. Read More

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Impact of Curcumin on Microsomal Enzyme Activities: Drug Interaction and Chemopreventive Studies.

Curr Med Chem 2021 Mar 29. Epub 2021 Mar 29.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad. Iran.

Curcumin, a yellow pigment in Asian spice, is a natural polyphenol component of Curcuma longa rhizome. Curcuminoid components include curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Previous studies established curcumin as a safe agent based on preclinical and clinical evaluations and curcuminoids have been approved by the US Food and Drug Administration (FDA) as "Generally Recognized as Safe" (GRAS). Read More

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Clinical treatment for hepatitis C reverses CYP2C19 inhibition.

Br J Clin Pharmacol 2021 Mar 19. Epub 2021 Mar 19.

Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

Aims: Infection by the hepatitis C virus (HCV) generates inflammatory response selectively modulating cytochrome P450 protein (CYP) activities. This study assessed the effect of chronic hepatitis C on CYP2C19 activity in patients with HCV.

Methods: Patients with HCV infection (n = 23) at different fibrosis stages were allocated into groups 1 (F0/F1 and F2, mild to moderate fibrosis) and 2 (F3 and F4, advanced fibrosis stages). Read More

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Modeling Approach to Predict the Impact of Inflammation on the Pharmacokinetics of CYP2C19 and CYP3A4 Substrates.

Pharm Res 2021 Mar 8;38(3):415-428. Epub 2021 Mar 8.

EA3738, Faculté de médecine de Lyon-Sud, Université de Lyon 1, 69921, Université de Lyon 1, Oullins cedex, France.

Purpose: For decades, inflammation has been considered a cause of pharmacokinetic variability, mainly in relation to the inhibitory effect of pro-inflammatory cytokines on the expression level and activity of cytochrome P450 (CYP). In vitro and clinical studies have shown that two major CYPs, CYP2C19 and CYP3A4, are both impaired. The objective of the present study was to quantify the impact of the inflammatory response on the activity of both CYPs in order to predict the pharmacokinetic profile of their substrates according to systemic C-reactive protein (CRP). Read More

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Design, synthesis and biological evaluation of 2-aminoquinazolin-4(3H)-one derivatives as potential SARS-CoV-2 and MERS-CoV treatments.

Bioorg Med Chem Lett 2021 05 2;39:127885. Epub 2021 Mar 2.

Center for Convergent Research of Emerging Virus Infection (CEVI), Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, South Korea; Korea University of Science and Technology, Daejeon 34114, South Korea. Electronic address:

Despite the rising threat of fatal coronaviruses, there are no general proven effective antivirals to treat them. 2-Aminoquinazolin-4(3H)-one derivatives were newly designed, synthesized, and investigated to show the inhibitory effects on SARS-CoV-2 and MERS-CoV. Among the synthesized derivatives, 7-chloro-2-((3,5-dichlorophenyl)amino)quinazolin-4(3H)-one (9g) and 2-((3,5-dichlorophenyl)amino)-5-hydroxyquinazolin-4 (3H)-one (11e) showed the most potent anti-SARS-CoV-2 activities (IC < 0. Read More

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In vitro and in silico studies of interaction of synthetic 2,6,9-trisubstituted purine kinase inhibitors BPA-302, BP-21 and BP-117 with liver drug-metabolizing cytochromes P450

Physiol Res 2020 12;69(Suppl 4):S627-S636

Department of Pharmacology, Faculty of Medicine, Palacký University Olomouc, Czech Republic.

An evaluation of possible interactions with enzymes of drug metabolism (cytochromes P450, CYP) is an important part of studies on safety and, in general, on the properties of any drug or biologically active compound. The article is focused on the preliminary metabolic study of selected 2,6,9-trisubstituted purine kinase inhibitors with significant anticancer activities which we have developed. The compounds BP-21 and BP-117 represent strong CDK inhibitors and the compound BPA-302 was developed as selective FLT3-ITD kinase inhibitor. Read More

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December 2020

Cyp33 binds AU-rich RNA motifs via an extended interface that competitively disrupts the gene repressive Cyp33-MLL1 interaction in vitro.

PLoS One 2021 19;16(2):e0237956. Epub 2021 Feb 19.

Department of Biochemistry, UCB 596, University of Colorado Boulder, Boulder, Colorado, United States of America.

Cyp33 is an essential human cyclophilin prolyl isomerase that plays myriad roles in splicing and chromatin remodeling. In addition to a canonical cyclophilin (Cyp) domain, Cyp33 contains an RNA-recognition motif (RRM) domain, and RNA-binding triggers proline isomerase activity. One prominent role for Cyp33 is through a direct interaction with the mixed lineage leukemia protein 1 (MLL1, also known as KMT2A) complex, which is a histone methyltransferase that serves as a global regulator of human transcription. Read More

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February 2021

Micropatterned Coculture With 3T3-J2 Fibroblasts Enhances Hepatic Functions and Drug Screening Utility of HepaRG Cells.

Toxicol Sci 2021 04;181(1):90-104

School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523, USA.

Human liver models are useful for assessing compound metabolism/toxicity; however, primary human hepatocyte (PHH) lots are limited and highly variable in quality/viability. In contrast, cell lines, such as HepaRG, are cheaper and more reproducible surrogates for initial compound screening; however, hepatic functions and sensitivity for drug outcomes need improvement. Here, we show that HepaRGs cocultured with murine embryonic 3T3-J2 fibroblasts, previously shown to induce PHH functions, could address such limitations. Read More

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Characterization of cytochrome P450s (CYP)-overexpressing HepG2 cells for assessing drug and chemical-induced liver toxicity.

J Environ Sci Health C Toxicol Carcinog 2021 ;39(1):68-86

Division of Biochemical Toxicology, National Center for Toxicological Research/U.S. FDA, Jefferson, Arkansas, USA.

Hepatic metabolism catalyzed by the cytochrome P450 (CYP) superfamily affects liver toxicity associated with exposures to natural compounds and xenobiotic agents. Previously we generated a battery of HepG2-derived stable cell lines that individually express 14 CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). In this study, we comprehensively characterized each cell line for its CYP expression and enzyme activity. Read More

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January 2021

Effects of Shengmai San on key enzymes involved in hepatic and intestinal drug metabolism in rats.

J Ethnopharmacol 2021 May 9;271:113914. Epub 2021 Feb 9.

Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan; Institute of Biopharmaceutical Sciences, School of Pharmacy, National Yang-Ming University, Taipei, Taiwan; Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address:

Ethnopharmacological Relevance: Shengmai San (SMS) has been commonly used as a traditional Chinese medicine for the treatment of cardiovascular disorders, of which drug interactions need to be assessed for the safety concern. There is little evidence for the alterations of hepatic and intestinal drug-metabolizing enzymes after repeated SMS treatments to assess drug interactions.

Aim Of The Study: The studies aim to illustrate the effects of repeated treatments with SMS on cytochrome P450s (CYPs), reduced nicotinamide adenine dinucleotide (phosphate)-quinone oxidoreductase (NQO), uridine diphosphate-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) using in vivo rat model. Read More

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A pharmacovigilance study of pharmacokinetic drug interactions using a translational informatics discovery approach.

Br J Clin Pharmacol 2021 Feb 5. Epub 2021 Feb 5.

Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA.

Background: While the pharmacokinetic (PK) mechanisms for many drug interactions (DDIs) have been established, pharmacovigilance studies related to these PK DDIs are limited. Using a large surveillance database, a translational informatics approach can systematically screen adverse drug events (ADEs) for many DDIs with known PK mechanisms.

Methods: We collected a set of substrates and inhibitors related to the cytochrome P450 (CYP) isoforms, as recommended by the United States Food and Drug Administration (FDA) and Drug Interactions Flockhart table™. Read More

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February 2021

Back where it belongs: 11β-hydroxyandrostenedione compels the re-assessment of C11-oxy androgens in steroidogenesis.

Mol Cell Endocrinol 2021 04 2;525:111189. Epub 2021 Feb 2.

Department of Biochemistry, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa; Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa. Electronic address:

Adrenal steroidogenesis has, for decades, been depicted as three biosynthesis pathways -the mineralocorticoid, glucocorticoid and androgen pathways with aldosterone, cortisol and androstenedione as the respective end products. 11β-hydroxyandrostenedione was not included as an adrenal steroid despite the adrenal output of this steroid being twice that of androstenedione. While it is the end of the line for aldosterone and cortisol, as it is in these forms that they exhibit their most potent receptor activities prior to inactivation and conjugation, 11β-hydroxyandrostenedione is another matter entirely. Read More

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Functional Analysis of Induced Human Ballooned Hepatocytes in a Cell Sheet-Based Three Dimensional Model.

Tissue Eng Regen Med 2021 04 30;18(2):217-224. Epub 2021 Jan 30.

Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, TWIns, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Background: Ballooned hepatocytes (BH) are a key histological hallmark of nonalcoholic steatohepatitis (NASH), yet their consequences for liver-specific functions are unknown.

Methods: In our previous study, an experimental model of human induced-BHs (iBH) has been successfully developed based on cell sheet technology. This study aimed to determine the functions of iBHs in the primary human hepatocyte/normal human dermal fibroblast (PHH/NHDF) co-culture cell sheets. Read More

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Modulatory effect of fructooligosaccharide against triphenyltin-induced oxidative stress and immune suppression in goldfish (Carassius auratus).

Ecotoxicol Environ Saf 2021 Apr 26;212:111966. Epub 2021 Jan 26.

College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang 471003, People's Republic of China.

Triphenyltin (TPT) is a widely used pesticide that is highly toxic to a variety of organisms, including humans, and is a potential contributor to environmental pollution. The present study was conducted to evaluate the oxidative stress and immunotoxicity induced by TPT in goldfish (Carassius auratus) and the protective effects of fructooligosaccharide (FOS). Goldfish (mean weight of 13. Read More

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Elucidation of plasma protein binding, blood partitioning, permeability, CYP phenotyping and CYP inhibition studies of Withanone using validated UPLC method: An active constituent of neuroprotective herb Ashwagandha.

J Ethnopharmacol 2021 Apr 16;270:113819. Epub 2021 Jan 16.

Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. Electronic address:

Ethnopharmacological Relevance: Withanone (WN), an active constituent of Withania somnifera commonly called Ashwagandha has remarkable pharmacological responses along with neurological activities. However, for a better understanding of the pharmacokinetic and pharmacodynamic behavior of WN, a comprehensive in-vitro ADME (absorption, distribution, metabolism, and excretion) studies are necessary.

Aim Of The Study: A precise, accurate, and sensitive reverse-phase ultra-performance liquid chromatographic method of WN was developed and validated in rat plasma for the first time. Read More

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Application of Individualized PBPK Modeling of Rate Data to Evaluate the Effect of Hemodialysis on Nonrenal Clearance Pathways.

J Clin Pharmacol 2021 Jun 16;61(6):769-781. Epub 2021 Feb 16.

Department of Pharmacy and Therapeutics, Center for Clinical Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.

The aim of this study was to apply individualized, physiologically based pharmacokinetic modeling of CO production rates (iPBPK-R) measured by the erythromycin breath test to characterize the effect of hemodialysis on the function of nonrenal clearance pathways in patients with end-stage renal disease. Twelve patients previously received C-erythromycin intravenously pre- and post-hemodialysis. Serial breath samples were collected after each dose over 2 hours. Read More

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Differential effects on human cytochromes P450 by CRISPR/Cas9-induced genetic knockout of cytochrome P450 reductase and cytochrome b5 in HepaRG cells.

Sci Rep 2021 Jan 13;11(1):1000. Epub 2021 Jan 13.

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.

HepaRG cells are increasingly accepted as model for human drug metabolism and other hepatic functions. We used lentiviral transduction of undifferentiated HepaRG cells to deliver Cas9 and two alternative sgRNAs targeted at NADPH:cytochrome P450 oxidoreductase (POR), the obligate electron donor for microsomal cytochromes P450 (CYP). Cas9-expressing HepaRG (vector control) cells were phenotypically similar to wild type HepaRG cells and could be differentiated into hepatocyte-like cells by DMSO. Read More

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January 2021

Anthraquinones inhibit cytochromes P450 enzyme activity in silico and in vitro.

J Appl Toxicol 2021 Jan 12. Epub 2021 Jan 12.

Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, Maryland, USA.

Anthraquinones exhibit various pharmacological activities (e.g., antioxidant and laxative) and are commonly found in consumer products including foods, dietary supplements, drugs, and traditional medicines. Read More

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January 2021

Tissue-specific expression and activity of cytochrome P450 1A and 3A in rainbow trout (Oncorhynchus mykiss).

Toxicol Lett 2021 May 8;341:1-10. Epub 2021 Jan 8.

Department of Food Science, Aarhus University, Aarhus N, Denmark.

Piscine cytochrome P450 (CYP) enzymes play an important role in the metabolism of xenobiotics. Xenobiotics often act as inducers of CYP1A1 and CYP3A expression and activity in fish. We compared constitutive mRNA expression of CYP1A1, CYP3A27, and CYP3A45 and catalytic activity of CYP1A (7-ethoxyresorufin-O-deethylation, EROD) and CYP3A-like (benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylation, BFCOD) enzymes in the following six rainbow trout tissues: liver, gill, heart, brain, intestine, and gonad. Read More

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Malaria-induced Alterations of Drug Kinetics and Metabolism in Rodents and Humans.

Curr Drug Metab 2021 ;22(2):127-138

Department of Biological Sciences, National School of Public Health, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.

Background: Infections and inflammation lead to a downregulation of drug metabolism and kinetics in experimental animals. These changes in the expression and activities of drug-metabolizing enzymes may affect the effectiveness and safety of pharmacotherapy of infections and inflammatory conditions.

Objective: In this review, we addressed the available evidence on the effects of malaria on drug metabolism activity and kinetics in rodents and humans. Read More

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January 2021

Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity.

Eur J Med Chem 2021 Feb 13;212:113097. Epub 2020 Dec 13.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China; China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province, 44 West Culture Road, 250012, Jinan, Shandong, PR China. Electronic address:

Encouraged by our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Herein, we report the design, synthesis and biological evaluation of a series of novel oseltamivir derivatives via the structural modifications at C-NH of oseltamivir targeting 150-cavity. Among them, compound 5c bearing 4-(3-methoxybenzyloxy)benzyl group exhibited the most potent activity, which was lower or modestly improved activities than oseltamivir carboxylate (OSC) against N1 (H1N1), N1 (H5N1) and N1 (H5N1-H274Y). Read More

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February 2021

Physiologically inspired culture medium prolongs the lifetime and insulin sensitivity of human hepatocytes in micropatterned co-cultures.

Toxicology 2021 02 24;449:152662. Epub 2020 Dec 24.

School of Biomedical Engineering, Colorado State University, Fort Collins, CO, United States; Department of Mechanical Engineering, Colorado State University, Fort Collins, CO, United States; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, United States. Electronic address:

Given significant species-specific differences in liver functions, cultures of primary human hepatocytes (PHHs) are useful for assessing drug metabolism and to mitigate the risk of drug-induced hepatotoxicity in humans. While significant advances have been made to keep PHHs highly functional for 2-4 weeks in vitro, especially upon co-culture with both liver- and non-liver-derived non-parenchymal cells (NPCs), the functional lifespan of PHHs is 200-400 days in vivo. Therefore, it is desirable to determine culture conditions that can further prolong PHHs functions in vitro for modeling chronic drug exposure, disease pathogenesis, and to provide flexibility to the end-user for staggering drug incubations across multiple culture batches. Read More

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February 2021

Preliminary assessment of pharmacokinetic drug-drug interactions of EST64401 and EST64514, two sigma-1 receptor antagonists.

Xenobiotica 2021 Apr 20;51(4):373-386. Epub 2021 Jan 20.

Early ADME, Drug Discovery and Preclinical Development, ESTEVE Pharmaceuticals, Barcelona, Spain.

EST64401 and EST64514 are two selective sigma-1 receptor ligands that showed a good profile in a lead optimization process for oral pain treatment. Their potential for pharmacokinetic-based drug-drug interactions was assessed to anticipate clinical interactions.Both compounds showed a low potential for CYP inhibition with percentages of inhibition <50% at 1 µM in recombinant human CYPs (CYP1A2, 2C9, 2C19, 2D6 and 3A4) and IC ≥75 µM for CYP3A4 and 2D6 in human liver microsomes. Read More

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Expression of cytochrome P450 isozyme transcripts and activities in human livers.

Xenobiotica 2021 Mar 28;51(3):279-286. Epub 2020 Dec 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.

Individual differences in cytochrome P450 (CYP) enzymes contribute to responses to drugs and environmental chemicals. The expression of CYPs is influenced by sex, age, and ethnicity. Human CYP studies are often conducted with human liver microsomes and liver cells to evaluate chemical induction and drug interactions. Read More

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