Article
Anesthesiology
Catherine Chanfreau-Coffinier, Sony Tuteja, Leland E. Hull, Sally MacDonald, Olga Efimova, Jill Bates, Deepak Voora, David W. Oslin, Scott L. DuVall, Julie A. Lynch
Summary: The response to analgesic therapy is influenced by various factors, including genetics and drug interactions. This study aimed to evaluate the potential impact of pharmacogenetic (PGx) testing on the care of Veterans with noncancer pain who were prescribed opioids metabolized by the CYP2D6 gene. The results showed that a significant proportion of patients were at an elevated risk for undesirable responses to their opioid medication based on predicted phenotypes and drug-drug interactions. However, CYP2D6 testing was infrequently used, and the results were mainly utilized to optimize antidepressant treatments rather than pain medications. The findings suggest that utilizing PGx testing along with consideration of phenoconversion may enhance the precision medicine approach to pain management in Veterans.
Review
Pharmacology & Pharmacy
Camille Lenoir, Victoria Rollason, Jules A. Desmeules, Caroline F. Samer
Summary: Inflammation has a specific impact on CYP activities, depending on the nature and severity of the underlying inflammatory disease. The drug-disease interactions can significantly affect drug pharmacokinetic parameters and clinical management. Resolution of inflammation may lead to normalization of CYP activity, but further research is needed to clarify some equivocal results.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Naoki Katayama, Keiichi Odagiri, Akio Hakamata, Chiaki Kamiya, Shinya Uchida, Shimako Tanaka, Naoki Inui, Noriyuki Namiki, Koichiro Tatsumi, Hiroshi Watanabe
Summary: This study investigated the impact of clopidogrel on the pharmacokinetics of selexipag and its active metabolite in 14 healthy Japanese volunteers. The results showed that co-administration of clopidogrel with selexipag did not affect selexipag's pharmacokinetics, but significantly increased the AUC(0-infinity) of ACT-333679. Furthermore, even when selexipag was administered 1 day after discontinuation of clopidogrel, there was still an increase in the AUC(0-infinity) of ACT-333679, indicating a persistent inhibitory effect of clopidogrel on CYP2C8.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xu Wang, Jingjing Fa, Yuanjin Zhang, Shengbo Huang, Jie Liu, Junqing Gao, Lina Xing, Zongjun Liu, Xin Wang
Summary: There is a potential interaction between Danshen tablet and rivaroxaban as the former inhibits the metabolism of the latter. This may be due to the strong inhibitory effects of Danshen tablet's components, particularly dihydrotanshinone I, on CYP enzymes. Therefore, drug monitoring and dosage adjustment are necessary when Danshen tablet and rivaroxaban are used simultaneously in clinical practice.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Plant Sciences
Zhen-Wei Yu, Guo-Dong Lou, Le-Le Ge
Summary: This study developed a rapid and accurate method for screening CYP inducers in a traditional Chinese medicine, Shenmai injection, by combining a PXR reporter gene assay and LC-TOF-MS analysis. Ethanol extract showed stronger PXR activity than aqueous extract, with methyl ophiopogonanone B and ginsenoside F2 identified as CYP inducers. The identification method used in this study was found to be suitable and effective for screening CYP inducers in herbal preparations.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Chase P. Monckton, Aidan Brougham-Cook, Kerim B. Kaylan, Gregory H. Underhill, Salman R. Khetani
Summary: The protein composition and stiffness of the liver's extracellular matrix collaboratively regulate the phenotype of primary human hepatocytes. Higher stiffness supports increased expression of albumin and HNF4 alpha, while the ECM protein composition significantly modulates PHH functions. Adaptation of ECM conditions to 96-well plates reveals novel regulations of functions and drug-mediated enzyme induction.
ADVANCED MATERIALS INTERFACES
(2021)
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
Multidisciplinary Sciences
Yan Ding, Huida Guan, Yingxuan Yan, Yan Chen, Cheng Huang
Summary: This study aimed to investigate the drug-drug interaction (DDI) of Nomilin (Nom) and Atorvastatin (Atv) in vivo. The pharmacokinetic and pharmacodynamic studies revealed that Nom can impact the pharmacokinetic profile and pharmacodynamic effect of Atv, leading to a lesser reduction in lipid levels of mice treated with the combination of Nom and Atv. Furthermore, Nom can increase the activity and expression levels of hepatic microsomal CYP3A11.
Article
Plant Sciences
Weiping Ji, Jiquan Shen, Bo Wang, Feifei Chen, Deru Meng, Shuanghu Wang, Dapeng Dai, Yunfang Zhou, Changxiong Wang, Quan Zhou
Summary: This study found that in rats, dacomitinib increases the AUC and T (max) of poziotinib, while decreasing its CL when orally administered. In vitro experiments showed that dacomitinib inhibits poziotinib in a mixed manner in CYP3A4 and CYP2D6. These findings suggest a potential drug-drug interaction between poziotinib and dacomitinib that clinicians should be aware of when readministering with poziotinib.
PHARMACEUTICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shuaibing Liu, Ziteng Wang, Eric Chan, Yibo Zhao, Jian Kang, Xiaojian Zhang, Xin Tian
Summary: Vicagrel, an antiplatelet drug candidate targeting platelet P2Y12 receptor, exhibits potent inhibitory effects on several enzymes, including CYP2B6, CYP2C19, and UGT1A6. Physiological-based pharmacokinetic simulation suggests no clinically significant drug-drug interactions between vicagrel and bupropion or S-mephenytoin.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Shaofeng Su, Hongxian Wu, Jingfan Zhou, Guangwei Yuan, Haibo Wang, Jie Feng
Summary: This study evaluated the metabolic kinetics of curcumin and germacrone in liver microsomes and cytochrome P450 enzymes, and found their potential role in anti-NSCLC cancer action. The results suggest the importance of considering drug-drug and drug-enzyme interactions in clinical medication.
Article
Biochemistry & Molecular Biology
Arianna Giorgetti, Sara Amurri, Giulia Fazio, Carla Bini, Laura Anniballi, Filippo Pirani, Guido Pelletti, Susi Pelotti
Summary: In toxicogenetics, an integrative approach to predict phenotype based on post-mortem genotyping of drug-metabolizing enzymes can explain the cause of death and manner of death. However, concomitant drug use may lead to phenoconversion, resulting in a mismatch between genotype and observed metabolic profile. This study evaluated the phenoconversion of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 drug-metabolizing enzymes in autopsy cases. Results showed a high rate of phenoconversion for all enzymes, with increased frequency of poor and intermediate metabolizers after phenoconversion. No association was found between phenotypes and cause/manner of death, indicating the need for further research in the post-mortem setting.
Article
Gastroenterology & Hepatology
Yedidya Saiman, Ting-Chin David Shen, Peder J. Lund, Victoria M. Gershuni, Cholsoon Jang, Shivali Patel, Sunhee Jung, Emma E. Furth, Elliot S. Friedman, Lillian Chau, Benjamin A. Garcia, Gary D. Wu
Summary: Germ-free mice are crucial in studying the gut microbiome, but the hepatic histone acetylation state is found to be relatively stable despite changes in microbiota. On the other hand, hepatic transcriptome is responsive to alterations in the gut microbiota.
Review
Pharmacology & Pharmacy
Aleksi Tornio, Anne M. Filppula, Janne T. Backman
Summary: Multimorbidity, polypharmacotherapy, and drug interactions are prevalent in the ageing population. Drug-drug interactions can have negative health impacts, requiring translational research approaches to fully characterize the mechanisms, clinical effects, and implications of CYP-mediated DDIs.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2022)
Article
Medicine, Research & Experimental
Zelma Faisal, Violetta Mohos, Eszter Fliszar-Nyul, Katerina Valentova, Kristyna Kanova, Beata Lemli, Sandor Kunsagi-Mate, Miklos Poor
Summary: The study investigated the interactions of five silymarin components and their sulfate metabolites with human serum albumin and CYP enzymes. The results showed that each compound tested formed stable complexes with albumin, and certain components/metabolites could inhibit CYP enzymes, with 2,3-dehydrosilychristin-19-O-sulfate exhibiting the strongest inhibitory effect on CYP3A4. Hence, caution should be exercised when administering high doses of silymarin concurrently with medications, as interactions may interfere with drug therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
