Article
Pharmacology & Pharmacy
Jinying Zhu, Yuqing Zhao, Lu Wang, Chen Zhou, Sufeng Zhou, Tao Chen, Juan Chen, Zeru Zhang, Ying Zhu, Sijia Ding, Feng Shao
Summary: The study aimed to develop a PBPK/PD model for midazolam rectal gel, ensure the PK/PD behavior in healthy adults, identify key factors for absorption, and support future clinical studies. Based on simulations, the recommended maximum dose is 15 mg, and a retention time longer than 3 hours is needed for optimal effects.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Microbiology
Devasha Redhi, Mwila Mulubwa, Liezl Gibhard, Kelly Chibale
Summary: The translation of a preclinical antimalarial drug development candidate to the clinical phases should be supported by rational human dose selection. A model-informed strategy based on preclinical data, which incorporates pharmacokinetic-pharmacodynamic (PK-PD) properties with physiologically based pharmacokinetic (PBPK) modeling, is proposed to optimally predict an efficacious human dose and dosage regimen for the treatment of Plasmodium falciparum malaria.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Laura Maria Fuhr, Fatima Zahra Marok, Maximilian Mees, Felix Mahfoud, Dominik Selzer, Thorsten Lehr
Summary: This study developed a PBPK/PD model of felodipine and its metabolite dehydrofelodipine for DDI predictions, successfully capturing their metabolic pathways and interactions with CYP3A4 perpetrators such as itraconazole, erythromycin, carbamazepine, and phenytoin.
Article
Biochemistry & Molecular Biology
Seung-Hyun Jeong, Ji-Hun Jang, Yong-Bok Lee
Summary: Rabeprazole is commonly used for the treatment of gastritis and gastric ulcers, but there is limited knowledge about its inter-individual variability. This study found that women have a delayed absorption and higher maximum plasma concentrations of rabeprazole compared to men. The population pharmacokinetic-pharmacodynamic modeling predicted that males would have higher efficacy in rabeprazole treatment.
Article
Pharmacology & Pharmacy
Guoliang Deng, Fan Yang, Ning Sun, Danhong Liang, Anfen Cen, Chen Zhang, Suiqin Ni
Summary: This study aimed to determine the plasma exposure to meropenem in patients with chronic kidney disease (CKD) and to investigate optimal dosing regimens. A PBPK model was established and successfully predicted the pharmacokinetics of meropenem in different populations. The dosing regimen of meropenem needs to be adjusted according to the renal function of CKD patients. For patients receiving hemodialysis, pharmacodynamic evaluations were performed for different periods to determine optimal dosing regimens.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Takeshi Matsumoto, Yusuke Masuo, Anna Tanaka, Toshifumi Kimura, Tadaaki Ioroi, Tatsuya Yamakawa, Hiromu Kitahara, Yukio Kato
Summary: This study aimed to quantitatively investigate the differences in antitumor efficacy between a liposomal gemcitabine formulation and conventional gemcitabine. The study found that the exposure of tumors to the active metabolite of gemcitabine was a critical factor in determining the antitumor efficacy. Physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models were constructed to analyze the differences between encapsulated and unencapsulated gemcitabine. The models revealed specific parameters that could serve as potential biomarkers for predicting the efficacy of the liposomal gemcitabine formulation.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Medicine, Research & Experimental
Ioannis Loisios-Konstantinidis, Jennifer Dressman
Summary: PBPK/PD modeling is widely used to predict in vivo drug performance, but there are challenges with regulatory acceptance, incomplete physiological understanding, and model validation, which can limit their translatability and predictive performance. Advances in GI physiology and mechanistic tools will play a key role in the future development of PBBM.
MOLECULAR PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Yoo-Kyung Song, Yun-Hwan Seol, Min Ju Kim, Jong-Woo Jeong, Hae-In Choi, Seung-Won Lee, Yoon-Jee Chae, Sunjoo Ahn, Young-Dae Gong, Kyeong-Ryoon Lee, Tae-Sung Koo
Summary: Supinoxin, a novel anticancer drug candidate, exhibited good permeability and dose-independent pharmacokinetics in rats. After oral administration, it showed modest absorption and high absolute oral bioavailability, mainly eliminated via NADPH-dependent phase I metabolism.
Article
Pharmacology & Pharmacy
Seung-Hyun Jeong, Ji-Hun Jang, Yong-Bok Lee
Summary: This study simulated the pharmacokinetics (PK) and pharmacodynamics (PD) of torsemide in different population groups and exposure scenarios using a human-scale physiologically-based PK-PD (PBPK-PD) model. The results showed the importance of considering disease groups in the clinical therapy of torsemide and the difficulty of predicting the proportion of pharmacodynamics solely based on the differences in pharmacokinetics among population groups.
Article
Pharmacology & Pharmacy
Carmen Flores-Perez, Luis Alfonso Moreno-Rocha, Juan Luis Chavez-Pacheco, Norma Angelica Noguez-Mendez, Janett Flores-Perez, Delfina Ortiz-Marmolejo, Lina Andrea Sarmiento-Arguello
Summary: This study proposes a pharmacokinetic-pharmacodynamic (PK-PD) population model for the use of midazolam in pediatric patients undergoing minor surgery. The results demonstrate that adequate sedation without adverse effects can be achieved at half the usual dose. Further research is needed to optimize dosing schedules and prevent potential adverse effects.
Review
Biology
Prashant Kumar, Darshan Mehta, John J. Bissler
Summary: Extracellular vesicles (EVs) are cell-derived structures that play an important role in intercellular communication and drug delivery. Physiologically based pharmacokinetic (PBPK) modeling can predict the behavior of EVs in the body and optimize drug delivery system design.
Article
Chemistry, Medicinal
Albert Tang
Summary: A variety of new recurrent neural networks (RNNs) were evaluated on modeling irregularly sampled PK/PD data and predicting PD data of unseen dosing regimens and dosing levels. The RNNs were able to model daily dose (QD) PK/PD and extrapolate to twice daily (BID) dose PD based on BID PK. However, extrapolating to unseen dose levels outside of the dose range for training proved to be challenging for all the RNNs tested. Only the GRUD demonstrated reasonable prediction results when extrapolating to unseen doses that were 3 or 10-fold outside the training doses. Overall, these new RNNs showed promise of integrating neural networks in PK/PD.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Frederico S. Martins, Peijuan Zhu, M. Tobias Heinrichs, Sherwin K. B. Sy
Summary: This study evaluated paediatric dosing regimens for meropenem plus fosfomycin against multidrug-resistant bacteria, using PBPK models and PD analyses to identify effective dosing regimens for Klebsiella pneumoniae and Pseudomonas aeruginosa.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Hongrui Liu, Yiqun Yu, Lu Liu, Chunyan Wang, Nan Guo, Xiaojuan Wang, Xiaoqiang Xiang, Bing Han
Summary: The aim of this study was to evaluate the effect of pharmacokinetic changes on the antihypertensive effect of nifedipine caused by the co-administration with apatinib. The results showed that the exposure changes of nifedipine caused by combination with apatinib had little impact on the changes of systolic blood pressure. Therefore, nifedipine could be used in combination with apatinib without dose adjustment in clinic.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Instruments & Instrumentation
Jordi Minnema, Sven Even F. Borgos, Neill Liptrott, Rob Vandebriel, Christiaan Delmaar
Summary: The use of nanobiomaterials in medicine is gaining popularity. This study implemented and parametrized a physiologically based pharmacokinetic (PBPK) model to better understand the biodistribution of two nanobiomaterials in rats. The results showed significant kinetic differences between the two materials, highlighting the need for tailored parametrization of PBPK models. These findings contribute to the establishment of a comprehensive database for predictive biodistribution modeling.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Review
Medicine, General & Internal
Berengere M. Dumotier
POSTGRADUATE MEDICAL JOURNAL
(2015)
Meeting Abstract
Pharmacology & Pharmacy
Berengere Dumotier, Martin Traebert, Gregory Friedrichs
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2015)
Review
Pharmacology & Pharmacy
Steven Whitebread, Berengere Dumotier, Duncan Armstrong, Alexander Fekete, Shanni Chen, Andreas Hartmann, Patrick Y. Muller, Laszlo Urban
DRUG DISCOVERY TODAY
(2016)
Meeting Abstract
Pharmacology & Pharmacy
Mark Deurinck, Ingrid Pruimboom, Haisong Ju, Berengere Dumotier, Martin Traebert
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2016)
Article
Toxicology
Lucie Pouche, Antonio Vitobello, Michael Roemer, Milica Glogovac, A. Kenneth MacLeod, Heidrun Ellinger-Ziegelbauer, Magdalena Westphal, Valerie Dubost, Daniel Philipp Stiehl, Berengere Dumotier, Alexander Fekete, Pierre Moulin, Andreas Zell, Michael Schwarz, Rita Moreno, Jeffrey T. J. Huang, Cliff R. Elcombe, Colin J. Henderson, C. Roland Wolf, Jonathan G. Moggs, Remi Terranova
TOXICOLOGICAL SCIENCES
(2017)
Article
Toxicology
Ingra Mannhardt, Alexandra Eder, Berengere Dumotier, Maksymilian Prondzynski, Elisabeth Kraemer, Martin Traebert, Klaus-Dieter Soehren, Frederik Flenner, Konstantina Stathopoulou, Marc D. Lemoine, Lucie Carrier, Torsten Christ, Thomas Eschenhagen, Arne Hansen
TOXICOLOGICAL SCIENCES
(2017)
Meeting Abstract
Toxicology
Axel Vicart, Jacqueline Kinyamu-Akunda, Steven Whitebread, Berengere Dumotier, Laszlo Urban, William Kluwe, Jonathan Moggs, Francois Pognan, Salah-Dine Chibout
TOXICOLOGY LETTERS
(2017)
Meeting Abstract
Pharmacology & Pharmacy
Steven Whitebread, Berengere Dumotier, Duncan Armstrong, Alexander Fekete, Elena Kutlina, Hong Jin, Laszlo Urban
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2017)
Article
Cardiac & Cardiovascular Systems
Nicolas Guerard, Pierre Jordaan, Berengere Dumotier
CARDIOVASCULAR TOXICOLOGY
(2014)
Review
Cardiac & Cardiovascular Systems
Berengere M. Dumotier
Article
Cardiac & Cardiovascular Systems
Luc M. Hondeghem, Karl Dujardin, Peter Hoffmann, Berengere Dumotier, Fred De Clerck
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2011)
Meeting Abstract
Pharmacology & Pharmacy
Berengere Dumotier, Martin Traebert, Haisong Ju, Friedrichs Greg
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2014)
Article
Pharmacology & Pharmacy
Magdalena Koziczak-Holbro, Dean F. Rigel, Berengere Dumotier, David A. Sykes, Jeffrey Tsao, Ngoc-Hong Nguyen, Julian Bosch, Marie Jourdain, Ludivine Flotte, Yuichiro Adachi, Michael Kiffe, Moise Azria, Robin A. Fairhurst, Steven J. Charlton, Brian P. Richardson, Estelle Lach-Trifilieff, David J. Glass, Thomas Ullrich, Shinji Hatakeyama
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2019)
Article
Toxicology
Pierre Jordaan, Berengere Dumotier, Martin Traebert, Paul E. Miller, Andre Ghetti, Laszlo Urban, Najah Abi-Gerges
Summary: This study evaluated the proarrhythmia risk and inotropic effects of Hydroxychloroquine and Azithromycin in a cardiomyocyte contractility-based model of the human heart. Hydroxychloroquine was found to have low proarrhythmia risk, while combined with Azithromycin at therapeutic concentration, the risk increased. Additionally, Hydroxychloroquine and Chloroquine decreased contractility, whereas Azithromycin abolished Hydroxychloroquine's contractility effect.
TOXICOLOGICAL SCIENCES
(2021)