Article
Agriculture, Dairy & Animal Science
Kouassi R. Kpodo, Atul Chaudhari, Lori L. Schreier, Katarzyna B. Miska, Monika Proszkowiec-Weglarz
Summary: This study found that probiotic supplementation did not negatively affect bile acid metabolism and enterohepatic circulation in broiler chickens, but these effects were age dependent. These findings can contribute to the improvement of probiotic usage as an alternative to antibiotics in broiler chickens.
Article
Biochemistry & Molecular Biology
Yuting Zhang, Huimin Chen, Wei Cong, Ke Zhang, Yimin Jia, Lei Wu
Summary: Heat stress can hinder the growth performance of broilers, leading to economic losses. The study found that chronic heat stress resulted in a decrease in total bile acids and an increase in cholic acid, chenodeoxycholic acid, and taurolithocholic acid in broilers. The expression of CYP8B1 and BSEP increased in the liver, while the expression of FGF19 decreased in the ileum of heat-stressed broilers. Significant changes in gut microbial composition were also observed, with the enrichment of Peptoniphilus being positively correlated with the increased serum level of taurolithocholic acid.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Gastroenterology & Hepatology
Junwei Xiang, Zhengyan Zhang, Hongyi Xie, Chengcheng Zhang, Yan Bai, Hua Cao, Qishi Che, Jiao Guo, Zhengquan Su
Summary: FXR, a nuclear receptor for bile acids, plays a key role in regulating metabolic pathways and improving various diseases. Bile acids link the intestine with the liver through the enterohepatic circulation, with different types of bile acids having diverse effects on the intestines, providing a foundation for new treatment methods.
Article
Biochemistry & Molecular Biology
Ling Huang, Junping Zheng, Guangjun Sun, Huabing Yang, Xiongjie Sun, Xiaowei Yao, Aizhen Lin, Hongtao Liu
Summary: It has been found that 5-aminosalicylic acid (5-ASA) can improve colitis symptoms by modulating gut microbiota and bile acid metabolism. In a mouse model, treatment with 5-ASA alleviated colitis symptoms, increased body weight and colon length, and reduced disease activity index and spleen index. Moreover, 5-ASA protected colonic tissues by suppressing inflammation and decreasing levels of tight junction, mucin, and water-sodium transport proteins, and it reshaped the gut microbiota community structure by promoting beneficial bacteria and reducing harmful bacteria. Additionally, 5-ASA improved abnormal bile acid metabolism through specific signaling pathways. However, the protective effect of 5-ASA was only observed in mice with normal gut microbiota, emphasizing the importance of gut microbiota in colitis treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Food Science & Technology
Hongxia Liu, Ohji Kohmoto, Ayana Sakaguchi, Shota Hori, Misuzu Tochigi, Koji Tada, Yeonmi Lee, Keidai Kikuchi, Satoshi Ishizuka
Summary: This study demonstrated the significance of taurocholic acid in proximal gut leakiness and ruled out the influence of secondary bile acids.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Review
Gastroenterology & Hepatology
Frans Stellaard, Dieter Luetjohann
Summary: Regulation of bile acid metabolism involves maintaining a constant pool size through synthesis to compensate for intestinal loss. Bile acids cycle through the enterohepatic circulation after meals, with processes involving feedback inhibition of synthesis. A biphasic diurnal expression pattern of bile acid synthesis has been observed in humans, but details of synthesis inhibition and activation mechanisms remain unknown.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Article
Nutrition & Dietetics
Kenta Maegawa, Haruka Koyama, Satoru Fukiya, Atsushi Yokota, Koichiro Ueda, Satoshi Ishizuka
Summary: The enterohepatic circulation of 12 alpha-hydroxylated bile acid is enhanced in rats fed a high-fat diet, and dietary supplementation of raffinose can normalize hepatic lipid accumulation by suppressing this circulation.
BRITISH JOURNAL OF NUTRITION
(2022)
Article
Microbiology
Chihyeok An, Hyeyeon Chon, Wanrim Ku, Sunho Eom, Mingyu Seok, Sangha Kim, Jaesun Lee, Daesung Kim, Sanghyuk Lee, Hoonsup Koo, Hyunjung Cho, Seungyun Han, Juik Moon, Miil Kang, Kihyun Ryu
Summary: Bile acids have antimicrobial properties and show different inhibitory effects on various microorganisms. They have low inhibitory activity on microbiota in the intestine and bile duct, but significantly inhibit flora in other organs.
Review
Biochemistry & Molecular Biology
Robin Durnik, Lenka Sindlerova, Pavel Babica, Ondrej Jurcek
Summary: This paper provides a systematic review on the transport processes and enterohepatic circulation of bile acids (BAs). It focuses on describing specific or less-specific BA transport proteins and their localization, and provides essential information about the properties, flow, metabolism, and functions of BAs. The transport processes are described step by step, accompanied by descriptions of major proteins involved, and spillage of BAs into systemic circulation and urine excretion are also discussed. The review also highlights the importance of less-studied areas in the development of BA-related drugs.
Article
Fisheries
Thomas W. O. Staessen, Marc C. J. Verdegem, Marit A. J. Nederlof, Ep H. Eding, Johan W. Schrama
Summary: The type of dietary non-protein energy source can affect the size and synthesis of the total body bile acid pool in rainbow trout. Feeding a starch diet results in a larger bile acid pool size and higher bile acid synthesis compared to a fat diet, despite higher faecal bile acid loss. This suggests a potential regulatory mechanism in response to dietary changes that warrants further investigation.
AQUACULTURE NUTRITION
(2021)
Article
Pharmacology & Pharmacy
Melissa Metry, Nathaniel D. A. Dirda, Jean-Pierre Raufman, James E. Polli, Joseph P. Y. Kao
Summary: Transport of bile acids within the enterohepatic circulation is critical for bile acid regulation. Deficiency of FGF19 leads to bile acid diarrhea. We attempted to use nitroxide-conjugated bile acids as MRI contrast agents, but found that they were not effective in vivo.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Review
Gastroenterology & Hepatology
Leilei Yu, Yaru Liu, Shunhe Wang, Qingsong Zhang, Jianxin Zhao, Hao Zhang, Arjan Narbad, Fengwei Tian, Qixiao Zhai, Wei Chen
Summary: Cholestasis is a condition characterized by abnormal bile production or excretion, which can have various causes with complex factors. A better understanding and distinction of cholestasis from different etiologies is essential and will provide theoretical support for the development of corresponding therapeutic drugs.
Article
Pharmacology & Pharmacy
Tao Jiang, Chuyun Xu, Huifang Liu, Muyi Liu, Minmin Wang, Jiarui Jiang, Guangji Zhang, Chuqi Yang, Jianbo Huang, Zhaohuan Lou
Summary: The study found that the ethanol extract of Linderae radix effectively reduced TC, TG, and LDL levels, alleviated liver injury, improved gut microbiota disturbance caused by a high-fat diet, and restored abnormal bile acid metabolism caused by hyperlipidemia.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jason M. Ridlon, Steven L. Daniel, H. Rex Gaskins
Summary: Bile acids are derived from cholesterol and function as detergents to solubilize lipids and remove cholesterol. They also act as signaling molecules in various tissues. The structures of bile acids were established in the early 20th century, and research has since differentiated primary from secondary bile acids. The formation of bile acids involves a multi-step, bifurcating pathway.
JOURNAL OF LIPID RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Chang Yin, Ruqing Zhong, Weidong Zhang, Lei Liu, Liang Chen, Hongfu Zhang
Summary: Bile acids have been found to play a role in the absorption of dietary fat and fat-soluble molecules, as well as acting as chemical signals by binding to cell membranes and nuclear receptors. Abnormal levels of bile acids have been linked to metabolic disorders such as nonalcoholic fatty liver disease, type 2 diabetes mellitus, and tumors. The interaction between gut microbiota and bile acids, as well as the alteration of bile acid metabolism, play a critical role in the pathogenesis of these chronic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Behavioral Sciences
Sharmila Das, Xiaohui Jiang, Wenlei Jiang, Renee Tung, Tricia Y. Ting, James E. Polli
Summary: This study examined whether there were differences in measures of personality, mood, outlook, and beliefs between patients with epilepsy who were considered generic brittle (GB) and those who were not. The results showed that these standardized measures did not differentiate GB patients from non-GB patients. This suggests that factors contributing to generic brittleness may not be captured by neuropsychiatry tests.
EPILEPSY & BEHAVIOR
(2022)
Article
Pharmacology & Pharmacy
Raqeeb Jamil, James E. Polli
Summary: This study quantitatively assessed the contributions of biorelevant media-mediated solubility and diffusivity on enhanced drug dissolution in FeSSGF and FeSSIF-V2. The results showed that the enhancement of solubility was attenuated by slow colloid diffusivity.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Raqeeb Jamil, James E. Polli
Summary: Through analysis of the sources of variation in dissolution using biorelevant media, it was found that location and operator were the most significant factors contributing to dissolution variability, with location having a greater impact compared to day and fabrication method.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Sophie Shubow, Qin Sun, Ai Len Nguyen Phan, Dana C. Hammell, Maureen Kane, Gary H. Lyman, Allan Gibofsky, Gary R. Lichtenstein, Zachary Bloomgarden, Raymond K. Cross, Sarah Yim, James E. Polli, Yow-Ming Wang
Summary: The approval and adoption of biosimilar products are crucial for controlling healthcare costs and providing affordable options for patients. However, biosimilar adoption in the United States has been slow, largely driven by payers rather than clinicians. To understand the barriers to biosimilar adoption, a virtual workshop was held, featuring the experiences and perspectives of leading academic clinicians. Educational efforts, including highlighting the rigor of clinical pharmacology studies and the benefits of biosimilars, can play a major role in improving biosimilar acceptance.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Chemistry, Medicinal
Asmita Adhikari, Paul R. Seo, James E. Polli
Summary: The study successfully predicted the in vivo absorption profile and biopharmaceutic performance of five drug products using a dissolution-hollow fiber membrane (D-HFM) system. The results demonstrated the potential of the D-HFM system in accurately predicting the absorption characteristics of solid oral dosage forms and assessing their biopharmaceutic risk.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Melissa Metry, Nathaniel D. A. Dirda, Jean-Pierre Raufman, James E. Polli, Joseph P. Y. Kao
Summary: Transport of bile acids within the enterohepatic circulation is critical for bile acid regulation. Deficiency of FGF19 leads to bile acid diarrhea. We attempted to use nitroxide-conjugated bile acids as MRI contrast agents, but found that they were not effective in vivo.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Medicinal
Luke Schenck, Paresma Patel, Ramesh Sood, Llorente Bonaga, Peter Capella, Olivier Dirat, Deniz Erdemir, Steven Ferguson, Cinzia Gazziola, Lindsey Saunders Gorka, Laurie Graham, Raimundo Ho, Stephen Hoag, Ephrem Hunde, Billie Kline, Sau (Larry) Lee, Rapti Madurawe, Ivan Marziano, Jeremy Miles Merritt, Sharon Page, James Polli, Mahesh Ramanadham, Mohan Sapru, Ben Stevens, Tim Watson, Haitao Zhang
Summary: This article summarizes the presentation summaries and discussion highlights from the M-CERSI Workshop on Co-processed API, which took place on July 13 and 14, 2022 at the University of Mary-land. The workshop focused on recent advancements in the use of co-processed active pharmaceutical ingredients to improve drug substance properties and manufacturing processes, and explored proposals for commercializing these technologies. Regulatory considerations, including classification and CMC documentation, were discussed, and breakout sessions were held for further discussion.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Medicinal
Naseem A. Charoo, Daud B. Abdallah, Daoud T. Ahmed, Bertil Abrahamsson, Rodrigo Cristofoletti, Peter Langguth, Mehul Mehta, Alan Parr, James E. Polli, Vinod P. Shah, Atsushi Kambayashi, Jennifer Dressman
Summary: This study investigated the feasibility of using the Biopharmaceutics Classification System (BCS) as a substitute for pharmacokinetic studies in human volunteers to evaluate the bioequivalence of immediate-release (IR) oral, solid dosage forms containing levocetirizine dihydrochloride. The properties of levocetirizine, such as solubility, permeability, dissolution profile, therapeutic uses, pharmacokinetics, and pharmacodynamics, were reviewed according to the BCS. The data unequivocally classified levocetirizine as BCS Class 1. Based on the wide therapeutic index and low risk of severe adverse effects, it was concluded that a BCS-based biowaiver can be implemented for products containing levocetirizine dihydrochloride, with specific requirements for excipients, data gathering methods, and in vitro dissolution.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Fang Wu, Youssef Mousa, Kimberly Raines, Chris Bode, Yu Chung Tsang, Rodrigo Cristofoletti, Hongling Zhang, Tycho Heimbach, Lanyan Fang, Filippos Kesisoglou, Amitava Mitra, James Polli, Myong-Jin Kim, Jianghong Fan, Banu S. Zolnik, Duxin Sun, Yi Zhang, Liang Zhao
Summary: This report summarizes the proceedings of day 2 sessions 1 and 3 of a 2-day public workshop titled Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches, sponsored by the FDA and CRCG. The workshop aimed to discuss the role of mechanistic modeling, particularly PBPK modeling and simulation, in product development and regulatory submissions. It also aimed to showcase case studies on the use of mechanistic modeling for bioequivalence assessment and establish best practices for its application. The report highlights the topics covered, including PBPK absorption models for oral products, the impact of food on bioequivalence, successful cases, challenges, and opportunities in the field.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Yuqing Gong, Peijue Zhang, Miyoung Yoon, Hao Zhu, Ameya Kohojkar, Andrew C. Hooker, Murray P. Ducharme, Jogarao Gobburu, Geraldine Celliere, Parmesh Gajjar, Bing V. Li, Raja Velagapudi, Yu Chung Tsang, Anna Schwendeman, James Polli, Lanyan Fang, Robert Lionberger, Liang Zhao
Summary: On November 30, 2021, the FDA and CRCG organized a virtual workshop to discuss the use of Model-Integrated Evidence (MIE) for assessing bioequivalence of long-acting injectable and implantable drugs. The workshop aimed to identify best practices and challenges in utilizing MIE for generic LAI products. The report summarizes presentations and discussions on topics such as alternative study designs, current progress in MIE utilization, and model validation strategies.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Andrew Babiskin, Fang Wu, Youssef Mousa, Ming-Liang Tan, Eleftheria Tsakalozou, Ross L. L. Walenga, Miyoung Yoon, Sam G. G. Raney, James E. E. Polli, Anna Schwendeman, Vishalakshi Krishnan, Lanyan Fang, Liang Zhao
Summary: The virtual workshop aimed to explore the regulatory utility of mechanistic modeling for supporting alternative approaches to bioequivalence. It shared the current state and best practices of mechanistic modeling, and introduced the concept of a Model Master File for better model sharing. The workshop enhanced participants' understanding of mechanistic models, established consensus on model validation, and clarified regulatory expectations for mechanistic modeling in drug applications.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ana L. Coutinho, Rodrigo Cristofoletti, Fang Wu, Abdullah Al Shoyaib, Jennifer Dressman, James E. Polli
Summary: In this study, a reliable method using reverse phase high performance liquid chromatography (RP-HPLC) was developed to measure the logP of drugs. Calibration curves at pH 6 and 9 were created using reference standards with well-established logP values, and the logP of twelve common drugs was measured. The results showed general agreement with other HPLC-based literature logP values, indicating the potential of this method to provide reliable logP values of commonly used drugs.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Editorial Material
Chemistry, Medicinal
M. Mehta, J. E. Polli, P. Seo, S. Bhoopathy, K. Berginc, K. Kristan, J. Cook, J. B. Dressman, H. Mandula, U. Munshi, R. Shanker, D. A. Volpe, J. Gordon, S. Veerasingham, J. Welink, S. Almeida, P. Gonzalez, D. Painter, Y. C. Tsang, J. Vaidyanathan, R. Velagapudi
Summary: This workshop, organized by the University of Maryland Center of Excellence in Regulatory Science and Innovation and the FDA, focused on generating and evaluating drug permeability data and facilitating the development of high-quality drug products globally. It included lectures, panel discussions, and breakout sessions covering various topics, such as permeability assessment, influencing factors, and future directions.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Editorial Material
Medicine, Research & Experimental
James E. Polli
MOLECULAR PHARMACEUTICS
(2023)
Review
Pharmacology & Pharmacy
Mirko Koziolek, Patrick Augustijns, Constantin Berger, Rodrigo Cristofoletti, David Dahlgren, Janneke Keemink, Paer Matsson, Fiona McCartney, Marco Metzger, Mario Mezler, Janis Niessen, James E. Polli, Maria Vertzoni, Werner Weitschies, Jennifer Dressman
Summary: This review discusses various methodologies used to determine drug permeability in the human gastrointestinal tract, including in vitro, in silico, and in vivo approaches. It highlights advancements in novel techniques such as computational approaches and gut-on-chip models. The review also explores the impact of permeability estimations on PK predictions and the importance of drug permeability in clinical studies.
