Article
Chemistry, Medicinal
Chang-Keun Cho, Pureum Kang, Hye-Jung Park, Yun Jeong Lee, Jung-Woo Bae, Choon-Gon Jang, Seok-Yong Lee
Summary: The study aimed to develop and validate physiologically based pharmacokinetic (PBPK) model of tamsulosin in different CYP2D6 genotypes using Simcyp (R) simulator. Results showed that genetic polymorphism can affect the pharmacokinetics of tamsulosin.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Pieter-Jan De Sutter, Phebe Rossignol, Lien Breens, Elke Gasthuys, An Vermeulen
Summary: This study aimed to compare the accuracy of two physiologically based pharmacokinetic (PBPK) methods and isometrical scaling in estimating the volume of distribution at steady state (Vss) in neonates. The results showed that isometrical scaling underestimated Vss in neonates, while both PBPK methods reduced the magnitude of underprediction. Among them, the P&T+ method demonstrated higher accuracy, while the R&R method exhibited lower accuracy.
Review
Medicine, Research & Experimental
Hinke Siebinga, Berlinda J. de Wit-van der Veen, Marcel D. M. Stokkel, Alwin D. R. Huitema, Jeroen J. M. A. Hendrikx
Summary: Physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PK) modelling approaches are not widely used in radiopharmaceutical development. However, these methods have great potential for understanding the pharmacokinetics and whole-body distribution of radiopharmaceuticals.
Review
Chemistry, Multidisciplinary
Om Anand, Xavier J. H. Pepin, Vidula Kolhatkar, Paul Seo
Summary: The use of physiologically based biopharmaceutics modeling (PBBM) to support drug product quality attributes is an evolving field with growing interest. Establishing an in vitro-in vivo link is crucial for achieving patient centric quality standards. While PBBM offers advantages, there are challenges that require further improvements. Collaboration between regulatory, industry, and academic fields can advance the field and deliver on the promises of PBBM in establishing patient centric quality standards.
PHARMACEUTICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Thayna Rocco Machado, Thiago Honorio, Thaisa F. Souza Domingos, Dailane da Silva Candido de Paula, Lucio Mendes Cabral, Carlos R. Rodrigues, Barbara A. Abrahim-Vieira, Alessandra Mendonca Teles de Souza
Summary: This study aims to develop pediatric physiologically based pharmacokinetic (PBPK) models of semaglutide to estimate the pharmacokinetic profile for subcutaneous injections in children and adolescents with healthy and obese body weights. The semaglutide PBPK model was successfully developed in adults and scaled to the pediatric population. The findings highlight the need for safe dosing regimens in pediatric diabetes treatment.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Di Wu, Min Li
Summary: Physiologically based biopharmaceutics modeling (PBBM) integrates physicochemical properties of drugs and formulation characteristics with physiological parameters to predict drug absorption and pharmacokinetics. Despite its wide applications, there are still obstacles to the use of PBBM in drug development.
PHARMACEUTICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Choong-Min Lee, Pureum Kang, Chang-Keun Cho, Hye-Jung Park, Yun Jeong Lee, Jung-Woo Bae, Chang-Ik Choi, Hyung Sik Kim, Choon-Gon Jang, Seok-Yong Lee
Summary: This study developed a physiologically based pharmacokinetic (PBPK) model of metoprolol related to CYP2D6 genetic polymorphism, providing a basis for personalized therapy with metoprolol.
ARCHIVES OF PHARMACAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
George A. Mystridis, Georgios C. Batzias, Ioannis S. Vizirianakis
Summary: This article constructs PBPK models for DOX using systems pharmacology approach and analyses eight plausible models based on existing data and two clinical case studies. The validation of the models supports their design and provides a basis for further research.
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
Pediatrics
Paola Coppola, Essam Kerwash, Susan Cole
Summary: PBPK modelling is widely used in medicine development and regulatory submissions, especially in studying drug pharmacokinetics during pregnancy. Physiological changes during pregnancy may have potential impact on drug pharmacokinetics, so qualified models are needed to support high-risk decisions.
FRONTIERS IN PEDIATRICS
(2021)
Review
Pharmacology & Pharmacy
Jean Dinh, Trevor N. Johnson, Manuela Grimstein, Tamorah Lewis
Summary: Physiologically based pharmacokinetic (PBPK) modeling is a useful approach for predicting drug pharmacokinetics, especially in under-studied populations like pediatrics. However, there are important knowledge gaps for neonatal PBPK models, resulting in uncertainty in the predictions.
Article
Chemistry, Medicinal
Chang-Keun Cho, Hye-Jung Park, Pureum Kang, Sungmin Moon, Yun Jeong Lee, Jung-Woo Bae, Choon-Gon Jang, Seok-Yong Lee
Summary: The study aimed to develop and validate a physiologically based pharmacokinetic (PBPK) model of meloxicam related to CYP2C9 genetic polymorphism, successfully simulating drug metabolism in different genotypes. The predicted exposures of meloxicam in CYP2C9*1/*3, CYP2C9*1/*13, and CYP2C9*3/*3 genotypes were increased compared to CYP2C9*1/*1 genotype. Through optimization of meloxicam dosing in different genotypes, the study is expected to contribute to reducing the risk of adverse events associated with meloxicam.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Tycho Heimbach, Filippos Kesisoglou, Jasmina Novakovic, Christophe Tistaert, Martin Mueller-Zsigmondy, Sivacharan Kollipara, Tausif Ahmed, Amitava Mitra, Sandra Suarez-Sharp
Summary: This article discusses five case studies on using physiologically based biopharmaceutics modeling (PBBM) to establish safe spaces for oral drug products. It explores the challenges and methods in developing safe spaces and highlights the need for more case studies to drive the development of best practices.
JOURNAL OF PHARMACEUTICAL SCIENCES
(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
Pharmacology & Pharmacy
Liang Zheng, Hongyi Yang, Andre Dallmann, Xuehua Jiang, Ling Wang, Wei Hu
Summary: A physiologically based pharmacokinetic (PBPK) model of olanzapine in pregnant women was developed and validated in this study. The model predicted that dose adjustment of olanzapine may not be necessary for pregnant women if effective treatment was achieved before pregnancy and fetal toxicity can be ruled out.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Eman El-Khateeb, Susan Burkhill, Susan Murby, Hamza Amirat, Amin Rostami-Hodjegan, Amais Ahmad
Summary: The study analyzes the advancement of PBPK modeling and simulation over the last 20 years, showing a significant growth rate and a preference for commercial specialized PBPK platforms. The major applications include study design, predicting formulation effects, and metabolic drug-drug interactions, which have increased in proportion over the years.
BIOPHARMACEUTICS & DRUG DISPOSITION
(2021)
Article
Pharmacology & Pharmacy
Zubida M. Al-Majdoub, Daniel Scotcher, Brahim Achour, Jill Barber, Aleksandra Galetin, Amin Rostami-Hodjegan
Summary: Translation modeling of local drug concentrations has seen a significant increase in the past decade. In relation to the kidney, these models serve as a bridge for understanding drug disposition. This study identified multiple enzymes and transporters in human kidney cortex samples, establishing an open database and revealing correlations between enzyme and transporter abundance and activity.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Eman El-Khateeb, Zubida M. Al-Majdoub, Amin Rostami-Hodjegan, Jill Barber, Brahim Achour
Summary: Model-based assessment of liver disease effects on drug pharmacokinetics requires quantification of changes in drug-metabolizing enzymes and transporters. Different proteomic methods were compared in this study to quantify proteins in liver tissue, revealing discordance in effects of cirrhosis on various metabolism-related proteins. Relative changes in enzymes and transporters were consistent across proteomic methods, with standard-based label-free methods showing less bias and more precision. The study demonstrated differences in protein expression in cirrhosis associated with different etiologies.
DRUG METABOLISM AND DISPOSITION
(2021)
Review
Pharmacology & Pharmacy
Yukiko Murata, Sibylle Neuhoff, Amin Rostami-Hodjegan, Hiroyuki Takita, Zubida M. Al-Majdoub, Kayode Ogungbenro
Summary: Drug development for the central nervous system (CNS) is challenging due to the complexity of the brain and the blood-brain barrier (BBB). In vitro brain systems have been evaluated, but their translation to human brain concentration profiles is still under development. Linking in vitro-to-in vivo extrapolation (IVIVE) strategies to physiologically based pharmacokinetic (PBPK) models of the brain can improve the prediction of drug concentrations in CNS components. This report summarizes the status and limitations of IVIVE-PBPK-linked models and suggests further research for better prediction of CNS drug disposition.
Article
Pharmacology & Pharmacy
Brahim Achour, Pauline Gosselin, Jean Terrier, Yvonne Gloor, Zubida M. Al-Majdoub, Thomas M. Polasek, Youssef Daali, Amin Rostami-Hodjegan, Jean-Luc Reny
Summary: Precision dosing strategies require considering individual variability in pharmacokinetics and pharmacodynamics. Liquid biopsy is a valuable new approach for early disease diagnosis. This study aimed to verify the correlation between expression measurements of certain enzymes and transporters in liquid biopsy with genotype and activity phenotype. Verifying liquid biopsy against activity phenotype is important for individualized modeling approaches.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Shawn Pei Feng Tan, Daniel Scotcher, Amin Rostami-Hodjegan, Aleksandra Galetin
Summary: There is increasing evidence that active tubular secretory clearance may not decline proportionally with the glomerular filtration rate in chronic kidney disease, which may lead to overestimation of renal clearance when using only glomerular filtration rate as an approximation. Consideration of this phenomenon is necessary for physiologically-based pharmacokinetic models and dose adjustment in severe kidney disease.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Jill Barber, Zubida M. Al-Majdoub, Narciso Couto, Areti-Maria Vasilogianni, Annika Tillmann, Sarah Alrubia, Amin Rostami-Hodjegan, Brahim Achour
Summary: This study evaluated the performance of three widely used label-free proteomic methods in quantifying enzymes and transporters in human liver microsomal samples. The findings showed that the HiN and iBAQ methods had good agreement in measuring absolute abundances, while the TPA method overestimated abundances. The relative abundance distribution of enzymes was similar among the three methods, but differences were observed with the TPA method in the case of transporters. The variability and between-sample relative quantification were consistent across methods. The study also demonstrated overall agreement between the HiN method and a standard protein in the samples.
DRUG METABOLISM AND DISPOSITION
(2022)
Article
Chemistry, Multidisciplinary
Sebastian Frechen, Amin Rostami-Hodjegan
Summary: Modeling and simulation are essential tools in drug development, with mechanistic modeling being the fastest growing field and physiologically based pharmacokinetic (PBPK) modeling being recommended for specific applications by regulatory agencies. Ensuring the credibility of PBPK tools, software platforms, and related models is a crucial discussion point, with many questions remaining on how to ensure credibility. This study provides guidance on quality assurance of PBPK platforms and executing PBPK studies.
PHARMACEUTICAL RESEARCH
(2022)
Article
Chemistry, Medicinal
Sarah Alrubia, Zubida M. Al-Majdoub, Brahim Achour, Amin Rostami-Hodjegan, Jill Barber
Summary: Crohn's disease affects the mucosal layer of the intestine, potentially leading to changes in the expression of intestinal enzymes and transporters, which can affect the bioavailability of orally administered drugs. A quantitative proteomic analysis of inflamed and non-inflamed ileum and colon tissues from Crohn's disease patients and healthy donors revealed significant reductions in the abundance of certain proteins in inflamed Crohn's ileum, while non-inflamed ileum showed greater changes compared to healthy tissue. Modeling will provide a better understanding of the variable effects of Crohn's disease on oral drug bioavailability.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Sarah Alrubia, Jialin Mao, Yuan Chen, Jill Barber, Amin Rostami-Hodjegan
Summary: This article reviewed the clinical data on the pharmacokinetics of orally administered drugs in Crohn's disease (CD) patients and conducted a meta-analysis of the systems parameters. The results showed no consistent trends in the changes in oral bioavailability in CD patients. The direction and magnitude of variation in drug kinetics in CD patients varied depending on the nature of the drug and its formulation. Highly active CD patients had significantly higher exposure to certain drugs compared to healthy volunteers. Quantification of DMETs in the intestine and liver and well-defined drug disposition studies are necessary in CD patients.
CLINICAL PHARMACOKINETICS
(2022)
Letter
Pharmacology & Pharmacy
Brahim Achour, Amin Rostami-Hodjegan
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Sam Mostafa, Thomas M. M. Polasek, Chad Bousman, Amin Rostami-Hodjegan, Leslie J. J. Sheffield, Ian Everall, Christos Pantelis, Carl M. J. Kirkpatrick
Summary: Studies that focus on individual covariates and ignore their interactions may not be adequate for model-informed precision dosing (MIPD). This study aimed to construct virtual twins (VTs) of real patients receiving clozapine with interacting covariates related to genetics and environment and to determine the impact of these interacting covariates on predicted clozapine plasma concentrations. The results showed that increasing covariate virtualization improved the accuracy and reliability of the prediction models.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Arham Jamaal Rajput, Hamza Khaled Abdelmajed Aldibani, Amin Rostami-Hodjegan
Summary: PBPK applications in the literature show a greater use of non-open source-code (NOSC) software compared to open source-code (OSC) alternatives. Understanding the rationale behind utilizing OSC software is important for PBPK modelers. This analysis aims to determine the impact of OSC software on the rise of PBPK and suggests the inclusion of rationale in future PBPK modeling reports.
BIOPHARMACEUTICS & DRUG DISPOSITION
(2023)
Article
Pharmacology & Pharmacy
Hamza Khaled Abdelmajed Aldibani, Arham Jamaal Rajput, Amin Rostami-Hodjegan
Summary: While the reproducibility of models in systems biology and quantitative systems pharmacology has received recent attention, the concept of 'reusability' has been neglected. This study defines 'reusability' in the context of physiologically-based pharmacokinetic (PBPK) models and examines the impact of open source-code versus non-open source-code (NOSC) software on the extent of reusability. The results show that the nature of the source-code significantly influences the external reusability of PBPK models, with NOSC models being more reusable compared to open source-code (OSC) models.
BIOPHARMACEUTICS & DRUG DISPOSITION
(2023)
Article
Pharmacology & Pharmacy
Shawn Pei Feng Tan, Marie-Emilie Willemin, Jan Snoeys, Hong Shen, Amin Rostami-Hodjegan, Daniel Scotcher, Aleksandra Galetin
Summary: Monitoring endogenous biomarkers is important in evaluating drug-drug interactions and changes in transporter activity in disease. In this study, a PBPK model for the biomarker 4-pyridoxic acid (PDA) was developed and verified. The model successfully predicted PDA plasma concentrations and renal clearance in healthy subjects and the increase in PDA plasma concentration in patients with CKD.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Xuezhi Zhuo, Vito Fodera, Per Larsson, Zarah Schaal, Christel A. S. Bergstrom, Korbinian Lobmann, Aleksei Kabedev
Summary: Our previous work demonstrated that beta-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for over 12 months. We further investigated the stabilization mechanisms by testing five other drug molecules and using experimental techniques and molecular dynamics simulations. The results showed that steric confinement, hydrogen bonding, and the glass transition temperature of the drug molecule play important roles in stabilizing ASDs with high drug loadings.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Sebastian Schmidt, Ulrike Holzgrabe
Summary: The binding of drugs to plasma proteins, such as human serum albumin (HSA), is crucial for determining pharmacokinetic parameters. This study investigated the enantioselective binding of S- and R-ketamine to HSA. It was found that ketamine has weak affinity to HSA, with no significant differences in binding behavior between the individual enantiomers and the racemate. The aromatic ring and N-methyl group were identified as the most strongly involved structural moieties in the binding of ketamine to HSA.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Yuchen Zhao, Han Wang, Lin Jin, Ziwei Zhang, Lianghu Liu, Mengqi Zhou, Xianzheng Zhang, Lingling Zhang
Summary: Interleukins (ILs) are important for communication between immune cells and non-immune cells, but dysregulation of ILs expression is a characteristic of autoinflammatory diseases. Drugs targeting ILs have significant clinical benefits, but may also cause adverse reactions. Fusion protein technology, with its ability to enhance therapeutic efficacy, has been explored for developing anti-inflammatory drugs. This review discusses the efficacy of fusion protein drugs developed with ILs or their receptors in treating autoinflammatory diseases, highlighting the potential of this technology in future anti-inflammatory drug development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Serena Bertoni, Elena Simone, Stefano Sangiorgi, Beatrice Albertini, Nadia Passerini
Summary: This study investigated the correlation between the structure and release properties of solid lipid microparticles (MPs) with different liquid additives. The additives accelerated the conversion of the unstable alpha-form of tristearin to the stable beta-polymorph and caused structural modifications in the MPs. The presence of additives prolonged the drug release in water and resulted in higher release profiles in biorelevant media. The findings suggest that the release behavior can be influenced by the polymorphism and supramolecular-level structural modification of lipid formulations containing crystal modifiers.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Juulia Jarvinen, Ahmed B. Montaser, Santosh Kumar Adla, Jukka Leppanen, Marko Lehtonen, Kati-Sisko Vellonen, Tuomo Laitinen, Aaro Jalkanen, William F. Elmquist, Juri Timonen, Kristiina M. Huttunen, Jarkko Rautio
Summary: This study attempted to alter the brain distribution pattern of Palbociclib by creating and assessing two novel prodrugs. Although the prodrug design did not significantly improve Palbociclib brain delivery, the study provides valuable insights for future prodrug development and drug delivery strategies targeting specific transporters.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Review
Pharmacology & Pharmacy
Miao Wang, Xinyu Ma, Shiyu Zong, Yaqiong Su, Rui Su, Hong Zhang, Yang Liu, Chunliu Wang, Ye Li
Summary: This article discusses the potential and limitations of nasal administration in central nervous system drug delivery. Nasal gel viscosity can alleviate the impact of nasal mucociliary clearance on drug delivery, and materials such as gellan gum, chitosan, carbomer, cellulose, and poloxamer can be used to prepare nasal gels.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Bjarke Strom Larsen, Eric Kissi, Liebert Parreiras Nogueira, Natalja Genina, Ingunn Tho
Summary: This study investigates the influence of drug load and polymer molecular weight on the structure of 3D printed tablets. The results show that drug load and polymer molecular weight have a significant impact on the porosity and size of the tablets, while the effect of drug load on the total porosity of the tablets is minimal.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Zhentao Qiao, Fuhang Wang, Dongjian Han, Yuansong Zhuang, Qingjiao Jiang, Yi Zhang, Miaomiao Liu, Quanxu An, Zhiwei Wang, Deliang Shen
Summary: In this study, it was demonstrated that periadventitial delivery of rapamycin-fibrin glue (RPM-FG) can inhibit intimal hyperplasia (IH) in a rat carotid artery injury model without compromising re-endothelialization. This provides a promising direction for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Neele Puhlmann, Rodrigo Vidaurre, Klaus Kuemmerer
Summary: Active pharmaceutical ingredients and their metabolites and transformation products are pollutants that can harm human and environmental health. Designing greener APIs is an effective strategy to address this issue. The drug discovery and development process can incorporate environmental parameters to achieve this design, and this process is highly flexible.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)