Article
Infectious Diseases
Iris K. Minichmayr, Vincent Aranzana-Climent, Lena E. Friberg
Summary: Pharmacokinetic/pharmacodynamic (PKPD) models are valuable tools for characterizing and translating antibiotic effects. These models provide a more accurate description of the time course of antibiotic effects, considering mechanistic knowledge of pathogens and drugs. This review provides a comprehensive overview of previously published PKPD models, highlighting their details and main development purposes.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Pharmacology & Pharmacy
Ilse R. Dubbelboer, Erik Sjogren
Summary: This report summarizes the current state of in silico models for describing and predicting subcutaneous drug absorption. A review of original articles published from 2010 onwards was conducted, identifying 18 physiologically based models. The findings showed significant improvements in the quantitative aspects of subcutaneous drug administration and absorption, while also highlighting the need for improvements in data translation and generalization of these models.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
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.
Article
Microbiology
Sara T. Elazab, Nahla S. Elshater, Yousreya H. Hashem, Nayera M. Al-Atfeehy, Eon-Bee Lee, Seung-Chun Park, Walter H. Hsu
Summary: The study assessed the pharmacokinetics/pharmacodynamics and tissue residues of spiramycin in chickens, providing recommendations for oral dosage and withdrawal period against M. synoviae infection in chickens.
Article
Clinical Neurology
Yun Kim, Anhye Kim, Jae-Yong Chung
Summary: A population PK/PD model was developed to characterize the delayed QT prolongation effect of escitalopram, with findings suggesting a relatively constant drug effect on QTc change over 24 hours post-dosing. The study provides useful information for monitoring electrocardiograms in patients receiving intensive care after drug administration.
JOURNAL OF AFFECTIVE DISORDERS
(2021)
Review
Veterinary Sciences
Longfei Zhang, Hongbing Xie, Yongqiang Wang, Hongjuan Wang, Jianhe Hu, Gaiping Zhang
Summary: Pharmacokinetic/pharmacodynamic (PK/PD) integration models are used to investigate the antimicrobial activity characteristics of drugs targeting pathogenic bacteria through comprehensive analysis of the interactions between PK and PD parameters. PK/PD models have been widely applied in the development of new drugs, optimization of the dosage regimen, and prevention and treatment of drug-resistant bacteria.
FRONTIERS IN VETERINARY SCIENCE
(2022)
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
Biology
Kiran Manjunatha, Nicole Schaaps, Marek Behr, Felix Vogt, Stefanie Reese
Summary: The persistence of in-stent restenosis pathology calls for the development of accurate computational models. This study enhances an existing finite element framework by incorporating endothelial effects and pharmacological influences, allowing for optimization of drug-eluting stent implantation parameters. The model provides insights into the effectiveness of drug embedment and release profiles and can serve as a tool for clinicians to personalize interventional procedures.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Beihong Ji, Ying Xue, Yuanyuan Xu, Shuhan Liu, Albert H. Gough, Xiang-Qun Xie, Junmei Wang
Summary: This study utilized in silico pharmacokinetic and pharmacodynamic modeling to predict the drug-drug interaction between oxycodone and diazepam. The results suggest that diazepam may compete with oxycodone at the binding pocket of opioid receptors, leading to a synergistic effect between the two drugs.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Virology
Aruni Jha, Melanie Doyle-Eisele, David Revelli, Trevor Carnelley, Douglas Barker, Shantha Kodihalli
Summary: Despite vaccination efforts, treatment tools are still necessary for COVID-19. COVID-HIGIV showed significant survival benefit in SARS-CoV-2 infected mice and had similar pharmacokinetic profiles in healthy and infected mice. These findings suggest that early administration of COVID-HIGIV may be an effective treatment for SARS-CoV-2 infection.
Article
Infectious Diseases
Yingying Hu, Qiong Wei, Xingchen Bian, Xinyi Yang, Jicheng Yu, Jingjing Wang, Haijing Yang, Guoying Cao, Xiaojie Wu, Jing Zhang
Summary: This study investigated the pharmacokinetics and safety of oral and intravenous lefamulin in healthy Chinese subjects, and evaluated the efficacy of the intravenous administration regimen. The results showed that lefamulin exhibited extensive distribution, and the PK parameters were consistent between oral and intravenous administration. The regimen was found to be microbiologically effective and well-tolerated.
Article
Medicine, Research & Experimental
Gregory Jones, Lingxue Zeng, Jonghan Kim
Summary: This study evaluated the absorption, distribution, and elimination of deferoxamine nanoparticles (DFO-NPs) in rats and found their potential in improving safety and efficacy. Predictive pharmacokinetic models were developed to describe the pharmacokinetics of DFO-NPs, providing information for preclinical development and clinical translation. Additionally, a novel mechanism of subcutaneous absorption directly into the systemic circulation was identified, offering a new strategy for enhancing drug exposure of nanotherapeutics.
MOLECULAR PHARMACEUTICS
(2023)
Review
Microbiology
Fernanda Wirth, Keli J. Staudt, Bibiana Araujo, Kelly Ishida
Summary: This review describes and discusses the main mammal animal models for PK and PD studies of antifungals used in cryptococcosis treatment. Alternative models and computational methods are also addressed. All approaches for PK/PD studies are relevant to investigating drug-infection interaction and improving cryptococcosis therapy.
FUTURE MICROBIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Larissa Gabriela Faqueti, Layzon Antonio Lemos da Silva, Gabriela Salim Gomes Moreira, Scheila Kraus, Gustavo dos Santos Catarina de Jesus, Luciana Aparecida Honorato, Bibiana Verlindo de Araujo, Adair Roberto Soares dos Santos, Teresa Dalla Costa, Maique Weber Biavatti
Summary: This study aimed to investigate the pre-clinical pharmacokinetics behavior and antinociceptive activity of 5'-methoxynobiletin (5'-MeONB). The results showed that 5'-MeONB exhibited one-compartment model in rats and mice plasma, with oral bioavailability ranging from 8 to 11%, and it demonstrated inhibitory effects on acute nocifensive behavior induced by formalin.
PHARMACEUTICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Shen Cheng, Susheel Kumar Nethi, Mahmoud Al-Kofahi, Swayam Prabha
Summary: Nano-engineered mesenchymal stem cells (nano-MSCs) are potentially effective targeted drug delivery platforms for treating solid tumors, but their pharmacokinetic-pharmacodynamic relationship requires quantitative description to optimize therapeutic efficacy. A mechanism-based preclinical PK-PD model was developed to characterize the PK-PD relationship of nano-MSCs in orthotopic A549 human lung tumors in SCID Beige mice, showing potential for improving anti-tumor efficacy with dosage adjustments and modulation of exocytosis rates.
Article
Chemistry, Multidisciplinary
Adam Paclawski, Jakub Szlek, Renata Jachowicz, Stefano Giovagnoli, Barbara Wisniowska, Sebastian Polak, Natalia Czub, Aleksander Mendyk
APPLIED SCIENCES-BASEL
(2020)
Article
Pharmacology & Pharmacy
Barbara Wisniowska, Zofia M. Bielecka, Sebastian Polak
Summary: The circadian rhythm of cardiac electrophysiology is influenced by various physiological and biochemical factors. Modeling and simulation studies can provide insights into heart chronotherapy questions. The study evaluated the performance of circadian models in Cardiac Safety Simulator v2.2 and found that electrolyte balance variability is the main factor influencing QT circadian pattern.
JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
(2021)
Article
Engineering, Manufacturing
Piotr Kulinowski, Piotr Malczewski, Edyta Pesta, Marta Laszcz, Aleksander Mendyk, Sebastian Polak, Przemyslaw Dorc
Summary: This paper presents a unique approach to 3D printing by Selective Laser Sintering of high dose controlled release pharmaceutical dosage form, using mainly crystalline paracetamol as a model drug substance. The study found that the functional properties, particularly dissolution performance, can be tuned by adjusting the active surface to volume ratio and pore space structure of the printlet. The flexibility and simplicity of preparation are highlighted as advantages of this approach.
ADDITIVE MANUFACTURING
(2021)
Article
Pharmacology & Pharmacy
Olha Shuklinova, Przemyslaw Dorozynski, Piotr Kulinowski, Zofia Bielecka, Barbara Wisniowska, Sebastian Polak
Summary: A PBPK model was developed to predict the pharmacokinetics of ropinirole in different patient populations, showing good accuracy in predicting PK parameters and being able to predict response in healthy volunteers, Parkinson's disease patients, and restless legs syndrome patients.
ACTA POLONIAE PHARMACEUTICA
(2021)
Article
Chemistry, Multidisciplinary
Przemyslaw Talik, Aleksander Mendyk
Summary: The study focused on investigating differently bound water molecules confined in hydrated hydroxypropyl cellulose (HPC) type MF, as well as their mixtures with lowly soluble salicylic acid and highly soluble sodium salicylate using differential scanning calorimetry (DSC). The ice-melting DSC curves were deconvoluted into multiple components to estimate the amounts of water in three states in the HPC matrix. The research also involved searching for an optimal number of Gaussian functions and discussing the results in detail, with assistance from AI/ML tools for theory elaboration.
APPLIED SCIENCES-BASEL
(2021)
Article
Pharmacology & Pharmacy
Natalia Czub, Adam Paclawski, Jakub Szlek, Aleksander Mendyk
Summary: Introduction of a new drug to the market is a challenging and resource-consuming process. Predictive models developed with the use of artificial intelligence could be the solution to the growing need for an efficient tool which brings practical and knowledge benefits, but requires a large amount of high-quality data. By developing a QSAR model and using automated machine learning methods, the affinity value for new molecules toward the 5-HT1A receptor can be efficiently predicted, potentially improving the process of drug discovery in the field of mental diseases and anticancer therapy.
Article
Pharmacology & Pharmacy
Jakub Szlek, Mohammad Hassan Khalid, Adam Paclawski, Natalia Czub, Aleksander Mendyk
Summary: This article presents an alternative machine learning approach to optimize the disintegration time of orally disintegrating tablets (ODTs). Various machine learning models are used to predict the disintegration time, and chemical descriptors representing the active pharmaceutical ingredient (API) characteristics are included. A deep learning model with good performance is obtained, and the critical parameters influencing disintegration are determined using the SHAP method.
Article
Pharmacology & Pharmacy
Jolanta Pyteraf, Adam Paclawski, Witold Jamroz, Aleksander Mendyk, Marian Paluch, Renata Jachowicz
Summary: Additive technologies, specifically 3D printing, have gained significant interest in pharmacy for producing personalized drugs. This study focuses on optimizing the process of manufacturing solid dosage forms using photopolymerization with visible light. By conducting pre-formulation studies and adjusting process parameters, the researchers successfully printed drug-loaded tablets with controlled release properties.
Article
Pharmacology & Pharmacy
Natalia Czub, Adam Paclawski, Jakub Szlek, Aleksander Mendyk
Summary: The study presents the best-in-class predictive model for the serotonin 1A receptor affinity and validates it according to OECD guidelines. This can help simplify the drug discovery and development process, improving efficiency.
Review
Pharmacology & Pharmacy
Justyna Srebro, Witold Brniak, Aleksander Mendyk
Summary: This review discusses the discovery and development of proton pump inhibitors (PPIs), formulation issues, and contemporary solutions, possibilities, and challenges in formulation development. It outlines the physicochemical characteristics of PPIs, their pharmacokinetic and pharmacodynamic properties, and stability, as well as qualitative and quantitative analysis methods. The review also characterizes commercial preparations with PPIs and focuses on the state of the art in the development of novel formulations with PPIs, covering various approaches employed in this process.
Article
Pharmacology & Pharmacy
Barbara Wisniowska, Susanne Linke, Sebastian Polak, Zofia Bielecka, Andreas Luch, Ralph Pirow
Summary: This study used a physiologically based pharmacokinetic (PBPK) model to simulate the dermal toxicokinetics of BPA and investigate its absorption through skin contact. Sensitivity analysis revealed factors influencing systemic exposure to BPA. The PBPK model was validated using serum BPA concentrations and revealed the temporary storage of BPA in the stratum corneum, providing insights for interpreting biomonitoring data and understanding the relationship between external and internal exposure measures.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Alicja Gawalska, Natalia Czub, Michal Sapa, Marcin Kolaczkowski, Adam Bucki, Aleksander Mendyk
Summary: Asthma and COPD are complex diseases involving chronic inflammation, bronchoconstriction, and airway remodeling. A potential solution to target these pathological processes is the development of multi-target-directed ligands (MTDLs) that inhibit PDE4B, PDE8A, and TRPA1. In this study, AutoML models were used to search for novel MTDL chemotypes blocking these biological targets. The results demonstrate the usefulness of AutoML methodology in identifying potential hits from large compound databases.
MOLECULAR INFORMATICS
(2023)
Article
Medicine, Research & Experimental
Natalia Czub, Jakub Szlek, Adam Paclawski, Klaudia Klimonczyk, Matteo Puccetti, Aleksander Mendyk
Summary: Oral medicines make up the largest pharmaceutical market area. Predicting drug absorption through the intestinal walls is crucial for candidate screening and reducing time to market. This study focuses on drug permeability and uses an AI-based system to accurately predict the absorption of serotonergic drugs. The proposed system shows promise as a tool for early-stage oral drug screening.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Krzysztof Woyna-Orlewicz, Witold Brniak, Wiktor Tatara, Magdalena Strzebonska, Dorota Haznar-Garbacz, Joanna Szafraniec-Szczesny, Agata Antosik-Rogoz, Kamil Wojteczko, Miroslaw Strozik, Mateusz Kurek, Renata Jachowicz, Aleksander Mendyk
Summary: Orodispersible tablets (ODTs) have been used for over 20 years to overcome the problem of swallowing solid dosage forms. In this research, we developed ODTs containing bromhexine hydrochloride that meet the registration requirements of the EMA. We examined the performance of five multifunctional co-processed excipients and a self-prepared physical blend of directly compressible excipients, and found that F-Melt and Ludiflash exhibited superior properties.
PHARMACEUTICAL RESEARCH
(2023)
Article
Computer Science, Information Systems
Barbara Wisniowska, Zofia Tylutki, Sebastian Polak