Article
Chemistry, Medicinal
Natalicia de Jesus Antunes, Fernanda de Lima Moreira, Karin Kipper, Lewis Couchman, Daniel Temponi Lebre, Atholl Johnston, Gilberto De Nucci
Summary: This study used static and dynamic approaches to predict dapaconazole clinical drug-drug interactions (DDIs) on main Cytochrome P450 (CYP) isoenzymes. The in vitro inhibition of dapaconazole on various CYP450 isoenzymes was evaluated, and a PBPK model was developed for humans. The analysis suggested that dapaconazole is a weak to strong inhibitor of different CYP isoenzymes depending on the clinical scenario.
Article
Plant Sciences
Nan Zhou, Yujie Zhu, Miaorong Hu, Rongyao Zheng, Mengqi Sun, Yueying Bian, Xijing Chen, Tingting Li
Summary: Picrorhiza scrophulariiflora, a Chinese herb, has antioxidant and anti-inflammatory effects. Picroside II, one of its active components, was found to modulate the activity of cytochrome P450 enzymes, potentially leading to herb-drug interactions. Careful monitoring is necessary when using Picroside II in combination with conventional drugs.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Electrochemistry
Celia M. Silveira, Patricia R. Rodrigues, Wissam Ghach, Sofia A. Pereira, Francisco Esteves, Michel Kranendonk, Mathieu Etienne, M. Gabriela Almeida
Summary: The study investigated the direct electrochemical response of membrane-bound human cytochrome P450 1A2 on pyrolytic graphite electrodes encapsulated in a sol-gel matrix. It showed that CYP1A2 is highly sensitive to O-2 and easily inactivated under aerobic conditions, but remains active when in the presence of its electron donor partner, cytochrome P450 oxidoreductase (CPR). This highlights the crucial role of CPR in stabilizing the immobilized CYP1A2 enzyme and preserving O-2 electrocatalysis in this electrochemical set-up.
Article
Pharmacology & Pharmacy
Yiran Wang, Jihua Shi, Dapeng Dai, Jianping Cai, Shuanghu Wang, Yun Hong, Shan Zhou, Fangling Zhao, Quan Zhou, Peiwu Geng, Yunfang Zhou, Xue Xu, Qingfeng Luo
Summary: This study evaluated the drug-drug interactions between vonoprazan and eleven common cardiovascular drugs through in vitro and in vivo experiments. The results showed that amlodipine and nifedipine inhibit the metabolism of vonoprazan and amlodipine affects vonoprazan's metabolism in vivo. Molecular simulation suggested that the CYP2B6 enzyme may play a larger role in vonoprazan's metabolism. Therefore, caution should be exercised when prescribing vonoprazan with cardiovascular drugs, especially amlodipine.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dimitrios Vagiannis, Youssif Budagaga, Anselm Morell, Yu Zhang, Eva Novotna, Adam Skarka, Sarah Kammerer, Jan-Heiner Kupper, Ivo Hanke, Tomas Rozkos, Jakub Hofman
Summary: This study evaluated the potential of tepotinib to modulate multidrug resistance and drug interactions, showing promising results in reversing drug resistance in cells with overexpressed ABC transporters. Tepotinib also demonstrated potent inhibition of ABCB1 and ABCG2 efflux transporters and various recombinant cytochrome P450 isoforms. These findings suggest a novel therapeutic strategy for future clinical investigations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Francisco Esteves, Cristina M. M. Almeida, Sofia Silva, Ines Saldanha, Philippe Urban, Jose Rueff, Denis Pompon, Gilles Truan, Michel Kranendonk
Summary: A unique cytochrome P450 (CYP) oxidoreductase (CPR) is important for maintaining the activities of human microsomal CYPs. The conformation of the CPR protein influences electron transfers and complex formation with CYPs. Mutations in the hinge region and FD domain of CPR can modulate CYP activities and regiospecificity of reactions in a substrate-dependent manner.
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)
Review
Chemistry, Medicinal
Yeo-Jung Kwon, Sangyun Shin, Young-Jin Chun
Summary: Human cytochrome P450 enzymes of the CYP1 family are critical in the metabolism of various substrates related to cancer pathogenesis and the pathogenesis of several human diseases, particularly in the activation and inactivation of therapeutic drugs. Their role in diseases and drug metabolism has attracted significant interest in the scientific community for the development of novel therapeutic strategies.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Zeyad Alehaideb, Mohamed Sheriffdeen, Francis C. P. Law
Summary: The study found that pre-treatment of volunteers with four ARFP extracts significantly inhibited caffeine metabolism, with increases in AUC(0-inf) ratio linearly related to the doses of furanocoumarins in the extracts. In vitro incubation studies showed that individual furanocoumarin bioactive compounds were potent inhibitors of caffeine-N-demethylation. CYP1A2 inactivation by these compounds was concentration- and time-dependent, involving irreversible inhibition mechanism.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Su Gwon Lee, Kwan Hyung Cho, Thi-Thao-Linh Nguyen, Dang-Khoa Vo, Yoon-Jee Chae, Han-Joo Maeng
Summary: This study investigates the inhibitory potential of 20(S)-Protopanaxadiol (20(S)-PPD) on cytochrome P450 enzymes (CYPs), which are important for drug pharmacokinetics. The results show that 20(S)-PPD strongly inhibits CYP3A4 and moderately inhibits CYP2B6 in human and mouse liver microsomes. Co-administration of 20(S)-PPD with specific substrates of these CYP enzymes alters the pharmacokinetics of the drugs. These findings suggest the need for careful attention when using 20(S)-PPD with other medications.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
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
Biochemistry & Molecular Biology
Manuel Sellner, Andre Fischer, Charleen G. Don, Martin Smiesko
Summary: Research using molecular dynamics simulations and protein-protein docking revealed the mechanism of conformational changes between cytochrome P450 enzymes and cytochrome P450 reductase, as well as proposed new conformational transition mechanisms and structural mechanisms for susceptibility to redox states.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Critical Care Medicine
Sheryl Wu, Heather B. Hoang, Jenny Z. Yang, Demosthenes G. Papamatheakis, David S. Poch, Mona Alotaibi, Sandra Lombardi, Cynthia Rodriguez, Nick H. Kim, Timothy M. Fernandes
Summary: The management of pulmonary arterial hypertension has become more complex due to increased pharmacotherapy options and longer patient survival. This review provides an overview of pharmaceutical metabolism and discusses important drug-drug interactions for approved medications in different pathways. Understanding these interactions is crucial for effective treatment.
Article
Chemistry, Multidisciplinary
Gustavo Perez Ortiz, John D. Sidda, Emmanuel L. C. de los Santos, Catherine B. Hubert, Sarah M. Barry
Summary: The antimycobacterial peptides rufomycins exhibit antibiotic activity due to oxidative tailoring of the cyclic peptide. Cytochrome P450s RufS and RufM play roles in regioselective epoxidation and alkyl oxidation, creating a complex product profile dependent on redox partner availability. Additionally, in vitro one pot conversion of rufomycin B to rufomycin C has been successfully demonstrated.
CHEMICAL COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jannarin Nontakham, Pongpun Siripong, Hitoshi Sato, Savita Chewchinda, Kuntarat Arunrungvichian, Jantana Yahuafai, Arman Syah Goli, Vilasinee Hirunpanich Sato
Summary: This study aimed to investigate the interactions between Triphala and cytochrome P450 (CYP) isoforms and P-glycoprotein (P-gp) through in vitro and in vivo experiments. The results showed that Triphala inhibited the activities of CYP1A and CYP3A, and increased the bioavailabilities of phenacetin and midazolam in rats.