Article
Pharmacology & Pharmacy
Meng Fu, Lin Luo, Sheng Feng, Hongda Lin, Zekun Lu, Fei Gu, Yang Fan, Bing Wu, Jianying Huang, Kai Shen
Summary: This study evaluated the effects of SHR0302 on the pharmacokinetics of cytochrome P450 (CYP) probe substrates. The results demonstrated that co-administration of SHR0302 did not have a clinically meaningful effect on the exposure of drugs metabolized by CYP3A4, CYP2C8, CYP2C9 and CYP2C19 in healthy subjects.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Nanna Tynelius, Christoffer Bundgaard, Claudia E. Mueller
Summary: Hepatocyte cocultures like HepatoPac have advantages in enzymatic activity over time, making them more frequently used for assessing the intrinsic clearance of slowly metabolised drugs. However, the high cost and practical limitations hinder the inclusion of quality control compounds in studies, resulting in the lack of monitoring of important metabolic enzymes. This study evaluates the use of a cocktail approach of quality control compounds in the human HepatoPac system to ensure adequate activity of major metabolising enzymes.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Kuo-Liang Wei, Guan-Lun Gao, Yu-Ting Chou, Chih-Yi Lin, Shan-Chun Chen, Yi-Ling Chen, Hui Qin Choi, Chi-Chia Cheng, Jyan-Gwo Joseph Su
Summary: This study demonstrates that sorafenib is a potent AhR antagonist, which can effectively suppress the growth of hepatocellular carcinoma and other cancers.
Article
Biochemistry & Molecular Biology
Ilia G. Denisov, Yelena V. Grinkova, Mark A. McLean, Tyler Camp, Stephen G. Sligar
Summary: Human cytochrome P450 CYP3A4 plays a significant role in the metabolism of more than 35% of pharmaceuticals, leading to drug-drug interactions. This study evaluated the use of midazolam as a probe substrate to detect and predict the involvement of new drug candidates in CYP3A4-mediated drug-drug interactions. The results suggest that the changes in the shape and volume of the substrate-binding pocket explain the occurrence of drug interactions.
Article
Biochemistry & Molecular Biology
Christopher S. Campomizzi, George E. Ghanatios, D. Fernando Estrada
Summary: Cytochromes P450 are versatile enzymes involved in endogenous and exogenous metabolism, undergoing structural changes related to function. This study demonstrates the utility of fluorine (19F)-NMR spectroscopy in monitoring structural changes in CYP121A1, revealing insights into its role in substrate recognition and mechanistic details of this essential enzyme from Mycobacterium tuberculosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Fabio Bachmann, Urs Duthaler, Stephan Krahenbuhl
Summary: This study investigated the effect of deglucuronidation on the plasma concentration of the constituents of the Basel phenotyping cocktail. The results showed that deglucuronidation of plasma samples improves the stability of phenotyping results and is necessary to reliably detect CYP induction.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Hongmei Su, Guo Feng, Qin Xu, Wei Li, Wen Liu, Zengguang Wu, Lailai Li, Wenjing Wang, Guanglin Zhu, Chenchen Ren, Xueli Song, Ju Zhang, Zhengyan He
Summary: The objective of this study was to investigate the effects of Radix Wikstroemia indica on six cytochrome P450 isozymes of rat liver microsomes before and after processing, and to study the mechanism of Radix Wikstroemia indica processed by the Sweat soaking method to reduce liver toxicity in rats. The results showed that processed Radix Wikstroemia indica could reduce liver injury, and its detoxification mechanism might be related to the decrease in enzyme activity of CYP1A2, CYP2E1, and CYP3A1.
LETTERS IN DRUG DESIGN & DISCOVERY
(2023)
Article
Pharmacology & Pharmacy
Can G. Leineweber, Miriam Rabehl, Anne Pietzner, Nadine Rohwer, Michael Rothe, Maciej Pech, Bruno Sangro, Rohini Sharma, Chris Verslype, Bristi Basu, Christian Sengel, Jens Ricke, Nils Helge Schebb, Karsten-H. Weylandt, Julia Benckert
Summary: Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and the medical treatment options are limited. The multikinase inhibitor sorafenib has been widely used for systemic therapy in advanced HCC. This study shows that sorafenib affects the levels of polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolites, indicating that specific supplementation with DHA could increase levels of the epoxy compound 19,20-EDP with potential anti-tumor activity in HCC patients receiving sorafenib therapy.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Amira Hussain, Declan P. Naughton, James Barker
Summary: This study examined the inhibitory potency of ibuprofen, remdesivir, and omeprazole on cytochrome P450 enzymes using rat liver microsomes in vitro. The results showed that ibuprofen acts as a non-competitive inhibitor, while remdesivir exhibits a mixed inhibition pattern, and omeprazole inhibits enzyme activity uncompetitively.
Article
Pharmacology & Pharmacy
Jinhui Wang, Feifei Chen, Hui Jiang, Jia Xu, Deru Meng, Peiwu Geng, Dapeng Dai, Jingbo Hu, Yunfang Zhou, Quan Zhou, Shuanghu Wang
Summary: Poziotinib is an irreversible pan-HER tyrosine kinase inhibitor used for the treatment of various cancers. It interacts with CYP enzymes, particularly inhibiting CYP2B1 and CYP2C11 activity in rats. This suggests the potential for drug interactions with these enzymes and the need for caution in clinical settings.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Richard P. McNeill, Mei Zhang, Michael J. Epton, Matthew P. Doogue
Summary: Severe COPD is associated with a clinically significant reduction in oral drug clearance, particularly for cytochrome P450 substrates. When prescribing for patients with severe COPD, reduced starting doses should be considered.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Myung-Eui Seo, Byung-Joo Min, Nayoon Heo, Kye Hwa Lee, Ju Han Kim
Summary: This study comprehensively assessed the drug metabolizing capabilities of CYP2C19 variants discovered through population sequencing and proposed a methodology that combines in silico prediction algorithms and functional assays to evaluate the changes in drug metabolism caused by genomic variants in CYP genes.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Physical
Lea R. Rapp, Sergio M. Marques, Erna Zukic, Benjamin Rowlinson, Mahima Sharma, Gideon Grogan, Jiri Damborsky, Bernhard Hauer
Summary: The cytochrome P450 CYP153A(M.aq) enzyme from Marinobacter aquaeolei was engineered to hydroxylate octanoic acid with significantly improved catalytic efficiency and substrate binding. The modifications in tunnel structures and loop regions were key in stabilizing the enzyme-substrate complex and enhancing catalytic efficiency. Previous fatty acid anchor interactions were also found to boost the enzyme activity towards octanoic acid.
Article
Pharmacology & Pharmacy
Haoqian Zhang, Furong Zhao, Yong Liu, Ying Li, Haiwen Liu, Hongzhi Sun
Summary: This research aimed to determine the inhibitory potential of eleven CPs on nine human CYP isoforms. The results showed that trichlorophenols, tetrachlorophenols, and PCP strongly inhibited CYP2C8 and CYP2C9, and clear structure-activity relationships of CPs on CYP2C8 were defined. Overall, CPs were found to cause inhibitory effects on CYP isoforms in vitro.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Punyabhorn Rattanacheeworn, Stephen J. Kerr, Wonngarm Kittanamongkolchai, Natavudh Townamchai, Suwasin Udomkarnjananun, Kearkiat Praditpornsilpa, Thanundorn Thanusuwannasak, Udomsak Udomnilobol, Suree Jianmongkol, Boonsri Ongpipattanakul, Thomayant Prueksaritanont, Yingyos Avihingsanon, Pajaree Chariyavilaskul
Summary: Aging and CKD can lead to reduced CYP3A activity and affect the metabolism of certain drugs. CKD may impact intestinal P-glycoprotein function, but further investigation is needed for confirmation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Peripheral Vascular Disease
Mohamed H. Shahin, Yan Gong, Caitrin W. McDonough, Daniel M. Rotroff, Amber L. Beitelshees, Timothy J. Garrett, John G. Gums, Alison Motsinger-Reif, Arlene B. Chapman, Stephen T. Turner, Eric Boerwinkle, Reginald F. Frye, Oliver Fiehn, Rhonda M. Cooper-DeHoff, Rima Kaddurah-Daouk, Julie A. Johnson
Article
Pharmacology & Pharmacy
Marina Kawaguchi-Suzuki, Negar Nasiri-Kenari, Jonathan Shuster, Fred G. Gmitter, Paul Cancalon, Felipe de Oliveria, Jennifer Kight, Eileen M. Handberg, Carl J. Pepine, Reginald F. Frye, Rhonda M. Cooper-DeHoff
JOURNAL OF CLINICAL PHARMACOLOGY
(2017)
Article
Endocrinology & Metabolism
Felipe A. de Oliveira, Mohamed H. Shahin, Yan Gong, Caitrin W. McDonough, Amber L. Beitelshees, John G. Gums, Arlene B. Chapman, Eric Boerwinkle, Stephen T. Turner, Reginald F. Frye, Oliver Fiehn, Rima Kaddurah-Daouk, Julie A. Johnson, Rhonda M. Cooper-DeHoff
Article
Endocrinology & Metabolism
Liming Weng, Yan Gong, Jeffrey Culver, Stephen J. Gardell, Christopher Petucci, Alison M. Morse, Reginald F. Frye, Stephen T. Turner, Arlene Chapman, Eric Boerwinkle, John Gums, Amber L. Beitelshees, Peggy R. Borum, Julie A. Johnson, Timothy J. Garrett, Lauren M. McIntyre, Rhonda M. Cooper-DeHoff
Article
Hematology
Stacy A. Voils, Stephen J. Lemon, Janeen Jordan, Paul Riley, Reginald Frye
THROMBOSIS RESEARCH
(2016)
Editorial Material
Pharmacology & Pharmacy
Mary W. Roederer, Grace M. Kuo, David F. Kisor, Reginald F. Frye, James M. Hoffman, Jean Jenkins, Kristin Wiisanen Weitzel
JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION
(2017)
Article
Cardiac & Cardiovascular Systems
Mohamed H. Shahin, Yan Gong, Reginald F. Frye, Daniel M. Rotroff, Amber L. Beitelshees, Rebecca A. Baillie, Arlene B. Chapman, John G. Gums, Stephen T. Turner, Eric Boerwinkle, Alison Motsinger-Reif, Oliver Fiehn, Rhonda M. Cooper-DeHoff, Xianlin Han, Rima Kaddurah-Daouk, Julie A. Johnson
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2018)
Article
Pharmacology & Pharmacy
Wen-Yi Li, Guo Yu, Renee M. Hogan, Rajesh Mohandas, Reginald F. Frye, Eric Gumpricht, John S. Markowitz
CLINICAL THERAPEUTICS
(2018)
Article
Hematology
Stacy A. Voils, Mohamed H. Shahin, Timothy J. Garrett, Reginald F. Frye
THROMBOSIS RESEARCH
(2018)
Article
Pharmacology & Pharmacy
Ahmed A. Albassam, Reginald F. Frye
SAUDI PHARMACEUTICAL JOURNAL
(2019)
Article
Pharmacology & Pharmacy
Stacy A. Voils, Bethany R. Shoulders, Sonal Singh, Laurence M. Solberg, Timothy J. Garrett, Reginald F. Frye
Article
Pharmacology & Pharmacy
Meghan J. Arwood, Caitrin W. McDonough, Larisa H. Cavallari, Amanda R. Elsey, Reginald F. Frye, Yan Gong, Taimour Langaee, Julie A. Johnson, Kristin Wiisanen
Summary: The study compared the effectiveness of a combined didactic and patient case-based teaching approach with a traditional didactic teaching strategy on students' knowledge and confidence in utilizing pharmacogenetic data. Results showed that the intervention group had significantly higher post-course knowledge and confidence scores compared to the control group. The combined teaching strategy improved students' ability to accurately self-assess their knowledge in pharmacogenetics.
JOURNAL OF THE AMERICAN COLLEGE OF CLINICAL PHARMACY
(2021)
Article
Pharmacology & Pharmacy
Cameron D. Thomas, Scott A. Mosley, Sarah Kim, Karthik Lingineni, Nihal El Rouby, Taimour Y. Langaee, Yan Gong, Danxin Wang, Siegfried O. Schmidt, Philip F. Binkley, David S. Estores, Kairui Feng, Hyewon Kim, Minori Kinjo, Zhichuan Li, Lanyan Fang, Arlene B. Chapman, Rhonda M. Cooper-DeHoff, John G. Gums, Issam S. Hamadeh, Liang Zhao, Stephan Schmidt, Reginald F. Frye, Julie A. Johnson, Larisa H. Cavallari
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2020)
Article
Gastroenterology & Hepatology
M. Kawaguchi-Suzuki, F. Bril, S. Kalavalapalli, K. Cusi, R. F. Frye
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2017)
Article
Biochemistry & Molecular Biology
Ahmed A. Albassam, Reginald F. Frye, John S. Markowitz
CHEMICO-BIOLOGICAL INTERACTIONS
(2017)