Article
Pharmacology & Pharmacy
Hinojal Zazo, Eduardo Lagarejos, Manuel Prado-Velasco, Sergio Sanchez-Herrero, Jenifer Serna, Almudena Rueda-Ferreiro, Ana Martin-Suarez, M. Victoria Calvo, Jonas Samuel Perez-Blanco, Jose M. Lanao
Summary: This study developed a physiologically-based pharmacokinetic (PBPK) model for gentamicin to explore dosing regimens in neonates. The model showed good predictive performance and demonstrated high efficacy and low toxicity in preterm and term neonates.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Lien Thi Ngo, Jaeyeon Lee, Hwi-yeol Yun, Jung-woo Chae
Summary: Tegoprazan is a novel P-CAB for the treatment of GERD and H. pylori infections. It is mainly metabolized by CYP3A4, so the investigation of DDI between tegoprazan and CYP3A4 perpetrators is crucial. Clarithromycin and rifampicin were selected as case studies to evaluate the DDI potential.
Article
Pharmacology & Pharmacy
Sandra Granana-Castillo, Maiara Camotti Montanha, Rachel Bearon, Saye Khoo, Marco Siccardi
Summary: This study investigated the drug-drug interaction between daily oral rilpivirine and daily or weekly rifapentine. The results showed that concomitant administration of rilpivirine and rifapentine led to a significant decrease in rilpivirine exposure, which could not be corrected by dose increment, thus coadministration should be avoided.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Gabriel Tao, Pavan Kumar Chityala, Li Li, Zhoumeng Lin, Romi Ghose
Summary: In this study, a new physiologically based pharmacokinetic (PBPK) model was established to predict the disposition kinetics of irinotecan. Bile excretion and UDP-glucuronosyltransferases (UGT) were found to play important roles in SN-38 pharmacokinetics. Inflammation significantly affected the metabolism of irinotecan.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Immunology
Sara Bettonte, Mattia Berton, Felix Stader, Manuel Battegay, Catia Marzolini
Summary: Strong inducers cannot be managed with long-acting cabotegravir and rilpivirine, while moderate inducers can be managed by adding daily oral rilpivirine to the monthly injection. Virtual clinical DDI studies using PBPK modeling provided recommendations for managing DDIs with rifampicin or rifabutin.
CLINICAL INFECTIOUS DISEASES
(2023)
Review
Pharmacology & Pharmacy
Miriam Ayuso, Laura Buyssens, Marina Stroe, Allan Valenzuela, Karel Allegaert, Anne Smits, Pieter Annaert, Antonius Mulder, Sebastien Carpentier, Chris Van Ginneken, Steven Van Cruchten
Summary: The use of neonatal and juvenile animal models, particularly pigs, in pediatric drug discovery and development shows promising potential for assessing drug safety and understanding disease mechanisms. However, limitations and unexplored aspects of this large animal model still need to be addressed for further development of nonclinical safety models for pediatric drug development.
Article
Chemistry, Medicinal
Muhammad Nasir Kalam, Muhammad Fawad Rasool, Faleh Alqahtani, Imran Imran, Asim Ur Rehman, Naveed Ahmed
Summary: This study aimed to understand the differences in propranolol pharmacokinetics between healthy and cirrhosis populations, using a whole-body PBPK model. The developed model effectively described propranolol disposition in both populations, with increased plasma concentration and decreased drug clearance observed in progressive stages of cirrhosis. This PBPK model can have implications in predicting propranolol dosing in cirrhosis patients with different disease severities.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Review
Pharmacology & Pharmacy
Kefei Wang, Kun Jiang, Xiaoyi Wei, Yulan Li, Tiejie Wang, Yang Song
Summary: The traditional method of calculating pediatric drug doses may result in overdose, while the physiologically based pharmacokinetic model provides a new approach for pediatric drug development. The article emphasizes the importance of establishing a pediatric PBPK model, and introduces various applications and related prospects of the model.
Article
Pharmacology & Pharmacy
Keyur R. Parmar, Pradeep B. Lukka, Santosh Wagh, Zaid H. Temrikar, Jiuyu Liu, Richard E. Lee, Miriam Braunstein, Anthony J. Hickey, Gregory T. Robertson, Mercedes Gonzalez-Juarrero, Andrea Edginton, Bernd Meibohm
Summary: Spectinamides 1599 and 1810 are being developed as potential treatments for multidrug-resistant and extensively drug-resistant tuberculosis. A physiologically based pharmacokinetic (PBPK) model has been developed to predict the pharmacokinetics of these compounds in various tissues, including those relevant to tuberculosis infection. The model accurately predicts the drug exposure in mice and rats, and can be used to optimize the dosing regimens.
Article
Pharmacology & Pharmacy
Bettina Gerner, Oliver Scherf-Clavel
Summary: The study developed a physiologically based pharmacokinetic model to accurately describe the pharmacokinetic behavior of Cabozantinib (CAB) under various conditions. The model successfully predicted plasma concentrations with low bias and good precision, and served as a basis for further simulations in special populations.
Article
Pharmacology & Pharmacy
Hafsa Hafsa, Ammara Zamir, Muhammad Fawad Rasool, Imran Imran, Hamid Saeed, Tanveer Ahmad, Sary Alsanea, Ali A. Alshamrani, Abdullah H. Alruwaili, Faleh Alqahtani
Summary: This study evaluated the pharmacokinetic differences after intravenous and oral administration of labetalol in healthy and diseased populations. A physiologically based pharmacokinetic (PBPK) model was developed to predict the drug disposition in patients with renal and hepatic diseases. The model was evaluated based on error calculations and box-whisker plots.
Article
Biochemistry & Molecular Biology
Muhammad Fawad Rasool, Stephanie Laeer
Summary: The PBPK model incorporating mechanism-based inhibition predicted the stereo-selective distribution of carvedilol accurately. The model showed close agreement between predicted and observed data, and can be used for exploring complex clinical scenarios.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2021)
Article
Pharmacology & Pharmacy
Radwan Ansaar, Robyn Meech, Andrew Rowland
Summary: This study investigated the factors influencing the metabolism pathway of epirubicin using in vitro experiments and a physiologically based pharmacokinetic model. The results showed that hepatic and renal UGT2B7 expression, plasma albumin concentration, age, BSA, GFR, haematocrit, and sex were the primary drivers of variability in epirubicin systemic exposure.
Article
Computer Science, Information Systems
Roberto Andrade, Jenny Torres, Ivan Ortiz-Garces, Jorge Mino, Luis Almeida
Summary: Software development is a rapidly expanding market that plays a pivotal role in various sectors such as healthcare, transportation, and finance. However, the field of cybersecurity has also experienced substantial growth, emphasizing the increasing importance of software security. The neglect of cybersecurity requirements during the initial phases of software development is a significant contributor to the subpar security quality and the persisting vulnerabilities or errors. This study aims to analyze the importance of integrating security modeling into the elicitation processes through the use of abuse stories, introducing a comprehensive and generic model for secure software development.
Article
Pharmacology & Pharmacy
Basile Amice, Harvey Ho, En Zhang, Chris Bullen
Summary: This research report presents a rare physiologically based pharmacokinetic (PBPK) model for the absorption, disposition, metabolism and excretion (ADME) of nicotine and its major metabolite cotinine in pregnant women. The model successfully reproduces the higher clearance rates of nicotine and cotinine in pregnant women compared to non-pregnant women, with simulation results showing temporal profiles for their disposition in organs such as the brain, including nicotine reaching its peak concentration within 2 minutes after intravenous injection. Further pharmacokinetic experiments are needed to refine clearance parameters for individual organs and the fetus.
FRONTIERS IN PHARMACOLOGY
(2021)