Article
Gastroenterology & Hepatology
Atousa Khalatbari, Zahra Aghazadeh, Cheng Ji
Summary: This study found that anti-COVID-19 drugs, especially when used in combination with other drugs or alcohol, cause cellular stress responses and injuries in liver cells.
HEPATOLOGY COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Marlies Oorts, Pieter Van Brantegem, Neel Deferm, Sagnik Chatterjee, Erwin Dreesen, Axelle Cooreman, Mathieu Vinken, Lysiane Richert, Pieter Annaert
Summary: Bosentan was evaluated at therapeutically relevant concentrations (2.5-25 μM) in sandwich-cultured human hepatocytes. It altered bile salt disposition and inhibited canalicular secretion of glycochenodeoxycholic acid (GCDCA). Within 24 hours, bosentan caused a shift from canalicular to sinusoidal efflux of GCDCA. These results also indicated reduced GCDCA formation. This study confirmed a direct effect of bosentan on chenodeoxycholic acid conjugation with glycine in liver S9 fraction.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Congrong Niu, Bill Smith, Yurong Lai
Summary: This study characterized the gene induction by ligands of CAR and AhR in human hepatocytes, showing distinct effects on metabolizing enzyme and drug transporter genes. Different inducers had varying degrees of effects on specific genes, highlighting the importance of assessing transporter gene inductions alongside metabolizing enzyme genes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Taleah Farasyn, Sonia Pahwa, Chao Xu, Wei Yue
Summary: This study demonstrates that pre-incubation with OATP1B inhibitors potentiates inhibitory effects in physiologically relevant primary human hepatocytes, supporting the rationale of the current US FDA draft guidance. IC50 values after inhibitor-preincubation in transporter-expressing cell lines may be used for DDI prediction for the purpose of mitigating false-negative OATP-mediated DDI prediction.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Ya-li Wu, Ya-ru Xue, Zi-tao Guo, Zhen-dong Chen, Xin-yu Ge, Da-fang Zhong, Xing-xing Diao
Summary: Furmonertinib has been identified as a potent CYP3A4 inducer, comparable to rifampin, making it a potential positive control for evaluating the induction potential of other drug candidates in preclinical studies. Results from the study show that furmonertinib induced CYP3A4 enzyme activity in a manner similar to rifampin in in vitro experiments.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Materials Science, Biomaterials
Nam V. Dao, Francesca Ercole, Yuhuan Li, Thomas P. Davis, Lisa M. Kaminskas, Erica K. Sloan, John F. Quinn, Michael R. Whittaker
Summary: The use of nanostructured carriers to improve the antioxidant activity of a typical nitroxide derivative, TEMPO, has shown promising results in reducing ROS levels in breast cancer-fibroblast co-cultures. The TEMPO-loaded star polymers have smaller sizes, better cell tolerance, and demonstrated effective scavenging activity against ROS, specifically targeting mitochondria during mitochondrial superoxide anion generation.
JOURNAL OF MATERIALS CHEMISTRY B
(2021)
Article
Microbiology
Jiantao Zhang, Qi Li, Shigehiro A. Kawashima, Mohamed Nasr, Fengtian Xue, Richard Y. Zhao
Summary: The study aimed to improve drug sensitivity in fission yeast and reduce the amount of drugs used. Three different methods affecting drug uptake were tested, and it was found that a mutant strain lacking key proteins regulating cellular efflux showed a significant increase in drug sensitivity.
Article
Pharmacology & Pharmacy
Taleah Farasyn, Chao Xu, Wei Yue
Summary: The study aimed to develop a novel rat SCH model expressing human OATP1B3 to study the hepatic disposition of OATP1B3 substrates. The results showed that expressing human OATP1B3 in rat SCH significantly increased the cellular accumulation of OATP1B3 substrates without affecting biliary excretion.
JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
(2021)
Article
Toxicology
Takashi Kitaguchi, Shinichiro Horiuchi, Yukie Kuroda, Katsutoshi Ohno, Kazuhiro Kobayashi, Mitsuru Tanaka, Seiichi Ishidaz
Summary: A simple in vitro culture method using cryopreserved human hepatocytes was developed to generate extended and functional bile canaliculi, and to evaluate the uptake and biliary excretion of compounds. Positive biliary excretion index (BEI) was observed for reported biliary-excreted compounds, while no difference in BEI was seen for a nonbiliary-excreted compound. Additionally, specific food-related compounds with reported biliary transporter involvement exhibited positive BEIs. This in vitro system can be used to predict the biliary excretion of pharmaceutical and food-related compounds.
JOURNAL OF TOXICOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Li Wei Ang, Oon Tek Ng, Irving Charles Boudville, Yee Sin Leo, Chen Seong Wong
Summary: Metabolic syndrome (MetS) is common in people living with HIV (PLHIV) in Singapore, with a prevalence of 23.6%. The most common metabolic abnormality is HDL hypocholesterolemia and hypertriglyceridemia. Regular monitoring, surveillance of drug effects, and behavioral interventions are needed for optimal management and prevention of metabolic disorders in PLHIV due to the long-term use of cART.
Article
Pharmacology & Pharmacy
Qian Yang, Albert P. Li
Summary: The study showed that while human hepatocytes underwent dedifferentiation after 2 days of culture, prolonged culturing resulted in redifferentiation based on gene expression. The observed redifferentiation suggests that prolonged (>7 days) culturing of human hepatocyte cultures may represent an experimental approach to overcome the initial dedifferentiation process.
DRUG METABOLISM AND DISPOSITION
(2021)
Article
Medicine, General & Internal
Caroline Schwarz, David Chromy, David Bauer, Nikki Duong, Victor Ulrich Schmidbauer, Michael Schwarz, Mattias Mandorfer, Armin Rieger, Michael Trauner, Michael Gschwantler, Thomas Reiberger
Summary: This study retrospectively assessed a group of 1458 HIV-infected patients and found that non-alcoholic fatty liver disease (NAFLD) is common in this population, and may be influenced by metabolic comorbidities and antiretroviral therapy (ART).
WIENER KLINISCHE WOCHENSCHRIFT
(2023)
Article
Pharmacology & Pharmacy
Nele Steenackers, Tim Vanuytsel, Patrick Augustijns, Ellen Deleus, Wies Deckers, Christophe M. Deroose, Gwen Falony, Matthias Lannoo, Ann Mertens, Raf Mols, Roman Vangoitsenhoven, Lucas Wauters, Bart Van der Schueren, Christophe Matthys
Summary: This study investigated the effects of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal motility, pH, and bile acid concentration. The findings showed that both surgeries increased pouch emptying and gastric emptying, and also led to higher pH levels and bile acid concentrations in the intestines. These results highlight the significant impact of these surgeries on gastrointestinal physiology.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Medicine, Research & Experimental
Albin Parrow, Per Larsson, Patrick Augustijns, Christel A. S. Bergstrom
Summary: In this study, coarse-grained molecular dynamics simulations were used to investigate the colloidal attributes and drug solubility in human intestinal fluids. The results showed the importance of glycerides in the formation of colloidal structures in the intestinal fluid. Additionally, the study revealed different types of colloidal structures and the impact of digestion and absorption on them. The simulation results were consistent with experimental solubilization data, highlighting the potential of coarse-grained molecular dynamics simulation in studying intestinal fluids.
MOLECULAR PHARMACEUTICS
(2023)
Article
Oncology
Getahun Befirdu Abza, Jemal Hussien Ahmed, Abdu Adem Yesufe, Edom Seife, Mengistu Erkie, Isabel Spriet, Legese Chelkeba, Pieter Annaert
Summary: Hepatitis B virus (HBV) is an important risk factor for hepatocellular carcinoma (HCC). The clinical conditions and survival of patients with HCC in Ethiopia are poor. Patients who received antiviral therapy had better survival outcomes than those who did not. Therefore, it is crucial to increase vaccination coverage and access to antiviral drugs against hepatitis to reduce the devastation of HCC.
Review
Pharmacology & Pharmacy
Cleo Demeester, Donnia Robins, Angela Elma Edwina, Jos Tournoy, Patrick Augustijns, Ibrahim Ince, Andreas Lehmann, Maria Vertzoni, Jan Frederik Schlender
Summary: The elderly population, as the fastest-growing demographic and major consumers of pharmaceutical products, present challenges in predicting drug safety and efficacy due to interindividual variability in the dose-exposure-response relationship. Current physiologically based pharmacokinetic (PBPK) models inadequately account for age-related changes in absorption. This review aims to summarize the physiological changes influencing oral absorption in older adults, discuss the capabilities of PBPK models in describing this population, and explore the impact of drug-drug interactions from polypharmacy on model development. Addressing identified gaps and integrating in vitro and in vivo data can enhance decision-making for formulation adequacy and pharmacotherapy in older adults.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Christer Tannergren, Harshad Jadhav, Emma Eckernas, Jonas Fagerberg, Patrick Augustijns, Erik Sjogren
Summary: This study evaluates the ability to predict regional differences in absorption and colon absorption in humans using mechanistic physiologically based biopharmaceutics modeling. The prediction performance is good for high permeability drugs but poor for low permeability drugs. The models need to be improved for more accurate predictions.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Tom de Waal, Joachim Brouwers, Maissa Rayyan, Cordula Stillhart, Liliya Vinarova, Zahari Vinarov, Patrick Augustijns
Summary: This study assessed the solubility of five poorly water-soluble, lipophilic drugs in intestinal fluid pools from 19 infant enterostomy patients. The solubilizing capacity of infant intestinal fluids was similar to that of adults, but the lipid phase of infant intestinal fluids played a significant role in drug solubilization. The huge variability in composition of infant intestinal fluid pools resulted in a highly variable solubilizing capacity.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Tom de Waal, Joachim Brouwers, Raf Mols, Ilse Hoffman, Maissa Rayyan, Patrick Augustijns
Summary: The composition of gastrointestinal fluids plays a crucial role in the absorption of orally administered drugs, and changes in fluid composition due to disease or age can affect drug pharmacokinetics. However, limited studies have been conducted on neonates and infants due to practical and ethical challenges. This study analyzed enterostomy fluids from neonates and infants, finding significant differences in fluid characteristics compared to adult intestinal fluids, which could impact drug absorption.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Zahari Vinarov, James Butler, Filippos Kesisoglou, Mirko Koziolek, Patrick Augustijns
Summary: Food-drug interactions pose challenges to oral drug development due to various factors. Bio-pharmaceutical assessment tools lack standardized settings and protocols. This article provides an overview of the approach and methodology used in food effect assessment and prediction, including in vitro dissolution-based predictions and physiologically based pharmacokinetic models. Animal models, particularly beagle dogs, also provide good predictions. Advanced formulation approaches can improve fasted state pharmacokinetics to decrease the difference in oral bioavailability between fasted and fed states. Regulatory approval of labeling instructions requires combining knowledge from various studies.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Julia Macente, Nina Nauwelaerts, Francesca M. Russo, Jan Deprest, Karel Allegaert, Bart Lammens, Rodolfo Hernandes Bonan, Jessica M. Turner, Sailesh Kumar, Andrea Diniz, Frederico S. Martins, Pieter Annaert
Summary: This study aims to use physiologically-based pharmacokinetic modeling to predict the maternal dose required for therapeutic fetal exposure in the treatment of congenital diaphragmatic hernia.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Tom de Waal, Joachim Brouwers, Philippe Berben, Talia Flanagan, Jan Tack, Wim Vandenberghe, Tim Vanuytsel, Patrick Augustijns
Summary: Parkinson's disease may not only impact the motor system but also the physiology of the gastrointestinal tract. The composition of intestinal fluids in PD patients is generally similar to healthy controls, with only minor differences. These differences may be attributed to slower gastric emptying and altered intestinal bacterial metabolism.
Letter
Gastroenterology & Hepatology
Mette Julsgaard, Uma Mahadevan, Thea Vestergaard, Raf Mols, Marc Ferrante, Patrick Augustijns
LANCET GASTROENTEROLOGY & HEPATOLOGY
(2023)
Review
Pharmacology & Pharmacy
Cordula Stillhart, Adam Asteriadis, Ekaterina Bocharova, Gabriel Eksteen, Fritz Harder, Jonas Kusch, Theodora Tzakri, Patrick Augustijns, Christophe Matthys, Maria Vertzoni, Werner Weitschies, Christos Reppas
Summary: The purpose of this review is to summarize the current knowledge on three physiological determinants of oral drug absorption in the advanced age population, namely gastric emptying, luminal fluid volume and composition, and intestinal permeability, in order to identify potential knowledge gaps and directions for further research efforts.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Medicine, Research & Experimental
Harshad Jadhav, Patrick Augustijns, Christer Tannergren
Summary: The rate and extent of colon absorption are important for the in vivo performance of extended-release (ER) drug products. This study evaluated different prediction approaches for ER drug product variants with different in vitro release profiles. The results showed that using the slowest ER variant improved prediction performance, regardless of colon absorption limitation.
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.
Correction
Pharmacology & Pharmacy
Matthias van der Veken, Michael Aertsen, Joachim Brouwers, Cordula Stillhart, Neil Parrott, Patrick Augustijns