Article
Microbiology
Vipul K. Gupta, Gary Maier, Leanne Gasink, Amanda Ek, Mary Fudeman, Praveen Srivastava, Angela Talley
Summary: Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral prodrug of tebipenem (TBP), which is effective against multidrug-resistant Gram-negative pathogens. The prodrug is converted to the active moiety TBP in the gastrointestinal tract. The main clearance pathways for elimination are through urine and feces, with TBP and its ring-open metabolite LJC 11562 being the major circulating metabolites in plasma.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Oncology
Thomas J. Semrad, Edward J. Kim, I-Yeh Gong, Tianhong Li, Scott Christensen, Mili Arora, Jonathan W. Riess, David R. Gandara, Karen Kelly
Summary: This study aimed to evaluate the safety and tolerability of the Aurora A kinase inhibitor alisertib in combination with weekly irinotecan. The results showed that adult patients were unable to tolerate the combination treatment at clinically meaningful doses due to hematologic and gastrointestinal toxicities.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2021)
Article
Oncology
Xiaofei Zhou, Farhad Sedarati, Douglas V. Faller, Dan Zhao, Helene M. Faessel, Swapan Chowdhury, Jayaprakasam Bolleddula, Yuexian Li, Karthik Venkatakrishnan, Zsuzsanna Papai
Summary: Pevonedistat, an investigational NEDD8-activating enzyme inhibitor, has shown activity in solid tumors and hematological malignancies. Clinical trials have demonstrated its relatively short half-life and preference for distribution in whole blood.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Pharmacology & Pharmacy
Rupeng Shi, Yi Chai, Hao Feng, Lijun Xie, Lulu Zhang, Tianqi Zhong, Juan Chen, Peng Yan, Bei Zhu, Jun Zhao, Chen Zhou
Summary: This study aimed to investigate the pharmacokinetics and safety of SHR8554 in healthy Chinese male subjects. The results showed that SHR8554 exhibited favorable pharmacokinetic characteristics and safety profiles, extensive metabolism, and primarily excreted through urine.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Oncology
Fei Guo, Bingyan Liu, Xiaoli Li, Haidong Wang, Xingyu Zhu, Yue Su, Cuixia He, Minhui Zhu, Jiaxiang Ding, Yuanyuan Xu, Xiangdi Zhao, Ying Wang, Rongfang Shan, Juan Zhu, Jing Xie, Qin Ge, Ling Fan, Yuzhou Ding, Yunqiu Xie, Chaoyang Zhang, Hongtao Li, Hongju Wang, Huan Zhou
Summary: In this study, the pharmacokinetics, mass balance, metabolism and excretion of SHC014748M in Chinese male subjects were investigated. The results showed that SHC014748M was absorbed, metabolized and excreted, with fecal excretion being the main elimination route.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Lu Wang, Lian Guo, Yixiang Wang, Renhua Guo, Zhaoqiang Xu, Zhengzhen Gao, Lijun Xie, Juan Chen, Ying Chen, Yun Liu, Hongwen Zhang, Lihua Bao, Wanhong Xu, Mingshe Zhu, Feng Shao, Yongqian Shu
Summary: The study found that in patients with advanced non-small cell lung cancer, abivertinib is primarily eliminated via the faecal route, and unchanged abivertinib plays a key role in the clearance and metabolism process in the body.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Brandi Lynn Soldo, Patrick Camilleri, Akshay Buch, John Janusz
Summary: The disposition of radioactivity following subcutaneous C-14-razuprotafib was explored in multiple species. The absorption and clearance of razuprotafib in human plasma are rapid, with majority of radioactivity recovered in feces within 24-48 hours. The CYP2C8 enzyme plays a significant role in razuprotafib metabolism, with different metabolites found in various species.
Article
Chemistry, Multidisciplinary
Yuan-dong Zheng, Hua Zhang, Yan Zhan, Yi-cong Bian, Sheng Ma, Hai-xian Gan, Xiao-juan Lai, Yong-qiang Liu, Yan-chun Gong, Xue-fang Liu, Hong-bin Sun, Yong-guo Li, Da-fang Zhong, Li-yan Miao, Xing-xing Diao
Summary: Vicagrel, a novel irreversible P2Y(12) receptor inhibitor, is being studied in phase III trials for acute coronary syndromes in China. This study found that vicagrel is rapidly absorbed, with metabolism primarily occurring on the thiophene ring, and renal elimination plays a crucial role in its disposition.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Pharmacology & Pharmacy
Minoru Tsuda, Kei Ogawa, Tadashi Endou, Takahiro Goto, Yuko Ogasawara, Akihito Ogasawara
Summary: Dersimelagon is a novel agonist for melanocortin 1 receptor being investigated for the treatment of erythropoietic protoporphyria, X-linked protoporphyria, and diffuse cutaneous systemic sclerosis (dcSSc). Studies in both humans and animals have shown that Dersimelagon is rapidly absorbed and eliminated, with a primary route of excretion being through feces. It is extensively metabolized in the liver and excreted in bile. These findings support the continued development of Dersimelagon for the treatment of photosensitive porphyrias and dcSSc.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2023)
Article
Oncology
Irene Vuu, Upendra P. Dahal, Zhe Wang, Xiaomeng Shen, John Rodgers, Jan Wahlstrom, Brett Houk
Summary: This study characterized the absorption, metabolism, and excretion of sotorasib in healthy male subjects. The results showed that sotorasib was rapidly absorbed and predominantly eliminated through fecal excretion. The study also identified the metabolites of sotorasib in plasma, urine, and feces.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2022)
Article
Biochemical Research Methods
Junjun Tian, Peng Lei, Yifei He, Ning Zhang, Xinyu Ge, Liqiang Luo, Shu Yan, Xingxing Diao
Summary: The study evaluated the metabolism and tissue distribution of 3-n-Butylphthalide in rats, finding that it was rapidly absorbed, widely distributed in various tissues throughout the body, mainly excreted through urine, and showed no gender differences in absorption, distribution, metabolism, and excretion.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2021)
Article
Oncology
Justin A. Chen, Jasmine C. Huynh, Chun-Yi Wu, Ai-Ming Yu, Karen Matsukuma, Thomas J. Semrad, David R. Gandara, Tianhong Li, Jonathan W. Riess, Kit Tam, Philip C. Mack, Anthony Martinez, Nichole Mahaffey, Karen L. Kelly, Edward J. Kim
Summary: The combination therapy of alisertib and gemcitabine shows potential for disease control in heavily pre-treated tumors, but gastrointestinal and hematologic toxicity is apparent.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yi-fei He, Yin Liu, Jing-hua Yu, Huan Cheng, Abdullajon Odilov, Fei-pu Yang, Guang-hui Tian, Xiu-mei Yao, Hua-qing Duan, Cheng-yin Yu, Chen Yu, Yan-mei Liu, Gang-yi Liu, Jing-shan Shen, Zhen Wang, Xing-xing Diao
Summary: TPN171 is a PDE5 inhibitor being tested for the treatment of PAH and ED in China. This study investigated its metabolic mechanism, pharmacokinetics, and clearance pathways in healthy Chinese male volunteers. TPN171 was rapidly absorbed, had a long half-life, and underwent extensive metabolism, primarily catalyzed by CYP3A4. One of its metabolites, a glucuronide metabolite of the O-dealkylated form, was found to be a significant component in human plasma.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Pharmacology & Pharmacy
Lin Xu, Chi-Chi Peng, Kate Dawson, Scott Stecher, James Woodworth, Chandra Prakash
Summary: Delayed-release dimethyl fumarate (DMF), also known as Tecfidera(R), is approved globally for the treatment of relapsing-remitting multiple sclerosis. After a single oral dose of [C-14]DMF, it was found that the majority of the drug is eliminated through expired air. Glucose is the main metabolite in the bloodstream, while cysteine and N-acetylcysteine conjugates of mono- and di-methyl succinate are the major metabolites in the urine. The metabolism of DMF involves hydrolysis, glutathione conjugation, and the tricarboxylic acid cycle.
Article
Oncology
Christos Fountzilas, Alex Adjei, Mateusz Opyrchal, Rachel Evans, Mohammad Ghasemi, Kristopher Attwood, Adrienne Groman, Wiam Bshara, Andrew Goey, John Wilton, Wen Wee Ma, Renuka Iyer
Summary: Ceritinib in combination with gemcitabine and gemcitabine/cisplatin has manageable toxicity profile, showing potential efficacy in tumors with ALK or ROS1 fusions.
INTERNATIONAL JOURNAL OF CANCER
(2021)
