Article
Pharmacology & Pharmacy
Rakshit S. Tanna, Dan-Dan Tian, Nadja B. Cech, Nicholas H. Oberlies, Allan E. Rettie, Kenneth E. Thummel, Mary F. Paine
Summary: Kratom's main alkaloid mitragynine has been shown to be a time-dependent inhibitor of hepatic and intestinal cytochrome P450 3A activity, potentially causing serious pharmacokinetic interactions with drugs. A static model predicted that mitragynine would increase systemic exposure to the probe drug midazolam by approximately 5.7-fold.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
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
Chemistry, Physical
Ying Wang, Baichun Hu, Yupeng Zhang, Dong Wang, Zhaohu Luo, Jian Wang, Fengjiao Zhang
Summary: The study found that the selectivity between CYP1A1 and CYP1B1 mainly depends on the sustainability of pi-pi stacking interactions with phenylalanine residues. Structural flexibility of protein domains orchestrates this interaction, determining binding selectivity. Modification of naphthoflavone compounds to satisfy pi-pi stacking interactions of key phenylalanine residues in CYP1B1 could improve inhibitory selectivity.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(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)
Review
Health Care Sciences & Services
Premalatha Balachandran, Mahmoud Elsohly, Kevin P. Hill
Summary: CBD, a non-intoxicating phytocannabinoid, has therapeutic effects and has been approved by the FDA for the treatment of two severe forms of pediatric epilepsy. Despite its widespread use for various indications, it can interact with common medications and substances such as acetaminophen and alcohol.
JOURNAL OF GENERAL INTERNAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Yasuhiro Yonezuka, Hiroki Kuwada, Hiromasa Imaishi
Summary: This study demonstrated the effectiveness of the P450 inhibition assay in a mouse model of DILI, suggesting its potential for diagnosing liver diseases such as acute DILI.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Pharmacology & Pharmacy
Yomna M. Nassar, Nicolas Hohmann, Robin Michelet, Katharina Gottwalt, Andreas D. Meid, Jurgen Burhenne, Wilhelm Huisinga, Walter E. Haefeli, Gerd Mikus, Charlotte Kloft
Summary: This study aimed to quantify the time course and extent of in vivo modulation of different CYP3A perpetrator drugs on hepatic CYP3A activity and distinguish different modulatory mechanisms by their time of onset, using pharmacologically inactive intravenous microgram doses of the CYP3A-specific substrate midazolam as a marker of CYP3A activity.
CLINICAL PHARMACOKINETICS
(2022)
Article
Pharmacology & Pharmacy
Song Ren, Karthick Vishwanathan, Mireille Cantarini, Paul Frewer, Indira Hara, Graeme Scarfe, Wendy Burke, Stein Schalkwijk, Yan Li, David Han, Ronald Goldwater
Summary: Co-dosing of rifampicin significantly reduces exposure to savolitinib, while co-dosing of itraconazole or midazolam with savolitinib has no clinically significant effect on PK. Co-dosing of famotidine with savolitinib reduces exposure to savolitinib, although this is not considered clinically meaningful. No new savolitinib-related safety findings were observed.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
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
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.
Review
Biochemistry & Molecular Biology
Joanna Jastrzebska, Wladyslawa Anna Daniel
Summary: Cytochrome P450 is involved in the metabolism of drugs, substances of abuse, and endogenous substrates. Cocaine affects the dopaminergic system and may also alter the regulation of cytochrome P450 during the addiction process. The effects of cocaine on liver cytochrome P450 enzymes depend on various factors and can lead to hepatotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Shawn Flanagan, Helen Walker, Voon Ong, Taylor Sandison
Summary: Rezafungin, a newly approved once-weekly echinocandin, has been shown to be free of severe drug-drug interactions (DDIs) according to extensive testing, making it a potential treatment for Candida infections and prevention of various infections.
MICROBIOLOGY SPECTRUM
(2023)
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
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
Dimitrios Vagiannis, Yu Zhang, Youssif Budagaga, Eva Novotna, Adam Skarka, Sarah Kammerer, Jan-Heiner Kuepper, Jakub Hofman
Summary: This study suggests that alisertib is a drug candidate with minimal potential for pharmacokinetic drug-drug interactions and multidrug resistance. Furthermore, alisertib has shown to enhance the effectiveness of anticancer drugs without impairing their activity in resistant cells. These findings provide important information for clinical use of alisertib.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)