Article
Multidisciplinary Sciences
Sarvesh Sabarathinam, Satish Kumar Rajappan Chandra, Vijayakumar Thangavel Mahalingam
Summary: The study found that the Maha yogaraja guggulu is a commonly used herbomineral polyherbal formulation that affects CYP3A4-mediated metabolism. Experimental results suggest that this formulation and its guggulsterone isomers may have drug interaction potential when used in combination with CYP3A4 substrates.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Stephen M. Stout, Carrie W. Nemerovski, Daniel S. Streetman, Melody Berg, Jamie Hoffman, Kayann Burke, Nina M. Bemben, Stephen J. Sklar
Summary: Agents that modify cytochrome P-450 (CYP) enzyme activity are categorized as strong, moderate, or weak inhibitors or inducers based on their impact on substrate exposure in clinical studies. However, limitations of data, inconsistent study findings, and other factors can complicate the assignment of agents to inhibitor or inducer categories. These categories are commonly used to differentiate drug interaction management recommendations, but ambiguity in classification may lead to harmful variations in clinical drug interaction management.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Jin Chen, Rowan Stringer, Bharti Shah, Jessie Gu, Yiming Zhang, Melissa Hackling, William Prince, Ralph Woessner
Summary: Tropifexor is a farnesoid X receptor agonist being developed for the treatment of nonalcoholic steatohepatitis. Drug-drug interaction studies showed that inhibition of UGTIA1 pathway has minor relevance for Tropifexor clearance, while CYP3A4 inhibition had a weak effect on Tropifexor PK. Inducing CYP3A4 with rifampin significantly decreased Tropifexor exposure. All coadministered drugs were well tolerated.
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT
(2022)
Article
Pharmacology & Pharmacy
Zhe Zhang, Xuehu Gao, Ping Zhang, Yuan Li, Meng Fu, Hongda Lin, Sheng Feng, Kai Shen, Guoning Yu, Xin Li
Summary: SHR0302, a selective JAK 1 inhibitor, is being investigated for the treatment of rheumatoid arthritis. Clinical studies showed that the CYP3A4 inducer rifampin and inhibitor itraconazole had an impact on the pharmacokinetics of SHR0302.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Martin Kondza, Mirza Bojic, Ivona Tomic, Zeljan Males, Valentina Rezic, Ivan Cavar
Summary: Flavonoids like chrysin can effectively inhibit the activity of the CYP3A4 enzyme, without showing pseudo-irreversible inhibition. While interacting with heme, no inhibitor-heme adducts were formed. These results suggest that flavonoids have the potential to inhibit CYP3A4 enzyme and interact with other drugs.
Article
Biochemistry & Molecular Biology
Seulgi Lee, Bernie Byeonghoon Park, Hongmok Kwon, Vitchan Kim, Jang Su Jeon, Rowoon Lee, Milan Subedi, Taehyeong Lim, Hyunsoo Ha, Dongju An, Jaehoon Kim, Donghak Kim, Sang Kyum Kim, Seyun Kim, Youngjoo Byun
Summary: This study confirmed that TNP selectively inhibits CYP3A4 in type I binding mode. By designing and synthesising TNP analogs and conducting biochemical studies, compound 9 was found to dramatically reduce CYP3A4 inhibition while retaining IP6K-inhibitory activity.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(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
Pharmacology & Pharmacy
Justin Q. Ly, Susan Wong, Liling Liu, Ruina Li, Kirsten Messick, Jae H. Chang
Summary: This study investigated the utility of transgenic mouse models in evaluating clinical induction, showing that they can reproduce clinical induction effects and differentiate tissue-dependent induction observed with different inducers. These results suggest the potential application of such transgenic models in assessing clinical induction and further investigating drug metabolism mechanisms.
DRUG METABOLISM AND DISPOSITION
(2021)
Review
Pharmacology & Pharmacy
A. David Rodrigues
Summary: Drug-drug interactions involving estrogen-containing oral contraceptives should consider metabolic enzymes in the gut and liver, emphasizing induction and inhibition profiles of CYP3A4/5, UGT1A1, and SULT1E1. New molecular entities (NMEs) should assess their therapeutic index and pharmacokinetic profile as potential victims of OC DDI, prioritizing, designing, and interpreting studies accordingly.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Yixin Hu, Jianyuan Wu, Bingyu Cheng, Rongli You, Xueyan Yin, Guiying Chen, Ling Yang, Yang Zhang, Luqin Si, Hongliang Jiang, Yongjun Zhang, Jianying Huang, Jiangeng Huang
Summary: Polymorphisms in the SLCO2B1 gene significantly affect the pharmacokinetic variability of ABI and its metabolites under both fasted and fed conditions. High-fat meal intake greatly increases the systemic exposure of ABI and its metabolites. The SLCO2B1 rs1077858 variant has a significant influence on the pharmacokinetic parameters of ABI, while other SLCO2B1 variants prolong the half-life of ABI. Polymorphisms in CYP3A4 and UGT1A4 do not significantly affect the pharmacokinetics of ABI and its metabolites.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
David Damoiseaux, Wenlong Li, Alejandra Martinez-Chavez, Jos H. Beijnen, Alfred H. Schinkel, Alwin D. R. Huitema, Thomas P. C. Dorlo
Summary: The use of the Cyp3aXAV mouse model for predicting human drug exposure, specifically for CYP3A4-metabolized small-molecule drugs, shows more accurate predictions compared to other models. This can lead to improved safety and efficacy in drug development, ultimately increasing the success rate.
Article
Plant Sciences
Qiwei Liu, Yunwen Xue, Jingjing Liu, Siqi Ren, Jie Xu, Jinni Yang, Yuanyue Xing, Zunjian Zhang, Rui Song
Summary: The study found that saikosaponins and saikogenins inhibit the catalytic activity and expression of CYP3A4 in a PXR-dependent manner, which may be highly related to the liver meridian guiding property of Radix Bupleuri.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Haixia Zhuang, Ying Ren, Chenyu Mao, Yueya Zhong, Zubin Zhang, Biyin Cao, Yuming Zhang, Jinqi Huang, Guoqiang Xu, Zhenqian Huang, Yujia Xu, Xinliang Mao
Summary: The zinc finger ubiquitin ligase RNF6 undergoes auto-ubiquitination mediated by its RING domain, and the process can be prevented by the deubiquitinating enzyme USP7. Anti-cancer drugs can induce polyubiquitination and degradation of RNF6, and reexpression of RNF6 can rescue drug-induced cell apoptosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Hong-can Ren, Yang Sai, Tao Chen, Chun Zhang, Lily Tang, Cheng-guang Yang
Summary: The study developed a PBPK-DDI model to predict drug-drug interactions co-administrated with ketoconazole in humans. Through verification with actual data, the model showed good predictive performance with predicted results within the observed range, and significantly better accuracy compared to traditional mechanistic models.
Article
Pharmacology & Pharmacy
Pan-Feng Feng, Long-Xun Zhu, Jing Jie, Peng-Xiang Yang, Xia Chen
Summary: The study revealed that berberine inhibits the transcription of CYP3A4 gene by downregulating nuclear receptor PXR, and accelerates the degradation of CYP3A4 protein via polyubiquitination pathway. These findings provide insights into the mechanisms of drug-drug interactions involving berberine.
CURRENT PHARMACEUTICAL DESIGN
(2021)