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.
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
Pharmacology & Pharmacy
Jan Grzegorzewski, Janosch Brandhorst, Matthias Koenig
Summary: The study focused on the metabolism of dextromethorphan (DXM) by cytochrome P450 2D6 (CYP2D6), utilizing a pharmacokinetics dataset and a physiologically based pharmacokinetic (PBPK) model to explore the impact of genetic polymorphisms in CYP2D6 on drug metabolism. The modeling approach considered drug-gene interactions, variability in enzyme activity, and the relationship between genotype and metabolic phenotype, providing insights into individual prediction of metabolic ratios. The findings offer a comprehensive understanding of CYP2D6 variability and its implications for personalized medicine.
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
Pharmacology & Pharmacy
Wei Wang, Defang Ouyang
Summary: PBPK modeling is a crucial tool to bridge drug properties and in vivo PK behaviors during drug development, especially in drug delivery systems. The simulation results provide important insights into new dosage forms, supporting drug regulation. However, practical challenges exist in applying this methodology.
DRUG DISCOVERY TODAY
(2022)
Review
Pharmacology & Pharmacy
Kiara Fairman, Miao Li, Baitang Ning, Annie Lumen
Summary: PBPK modeling is a powerful tool with potential applications in the development of RNAi therapeutics, a class of drugs with unique pharmacokinetic properties. While there is active research in this area, there are still challenges to fully evaluating the utility of PBPK models for RNAi therapeutics. The current computational modeling approaches can support efficient development and approval of RNAi therapeutics, but further exploration and standardization are needed to optimize their use.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Eleftheria Tsakalozou, Khondoker Alam, Andrew Babiskin, Liang Zhao
Summary: Physiologically-based pharmacokinetic (PBPK) modeling and simulation is used to predict the pharmacokinetics of drugs, particularly in the skin following topical application. These models can help regulators and product developers identify factors affecting local and systemic exposure. In the generic drug field, the use of dermal PBPK modeling to support alternative bioequivalence approaches is increasing. This report discusses the scientific considerations for the development, verification, and validation (V&V) of PBPK models for dermatological drug products.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Qiuyu Jia, Qingfeng He, Li Yao, Min Li, Jiaying Lin, Zhijia Tang, Xiao Zhu, Xiaoqiang Xiang
Summary: This paper summarizes the current situation and shortcomings of pharmacokinetic research on natural medicine and introduces the concept and advantages of PBPK modeling in the study of natural medicine pharmacokinetics.
Article
Chemistry, Medicinal
Sang-Sup Whang, Chang-Keun Cho, Eui Hyun Jung, Pureum Kang, Hye-Jung Park, Yun Jeong Lee, Chang-Ik Choi, Jung-Woo Bae, Hyung Sik Kim, Choon-Gon Jang, Seok-Yong Lee
Summary: This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of flurbiprofen related to CYP2C9 genetic polymorphism and describe its pharmacokinetics in different genotypes. The model successfully predicted the pharmacokinetics of flurbiprofen and could guide tailored drug administration strategy in various clinical scenarios.
ARCHIVES OF PHARMACAL RESEARCH
(2022)
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
Pharmacology & Pharmacy
Barbara Sanchez-Dengra, Isabel Gonzalez-Alvarez, Marival Bermejo, Marta Gonzalez-Alvarez
Summary: This study developed a new in vitro system combined with a PBPK model to predict brain concentration levels of different drugs in rats. Through internal validation, it was concluded that the model, incorporating MDCK data, provided the best predictions for passive diffusion and carrier-mediated transported drugs.
Article
Pharmacology & Pharmacy
Lingling Ye, Xiang You, Jie Zhou, Chaohui Wu, Meng Ke, Wanhong Wu, Pinfang Huang, Cuihong Lin
Summary: A PBPK model was used to assess the pharmacokinetics of daptomycin in children with renal impairment, showing increased exposure levels in children with varying degrees of renal impairment, indicating the need for further dose adjustments of daptomycin.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Elena O. Kutumova, Ilya R. Akberdin, Ilya N. Kiselev, Ruslan N. Sharipov, Vera S. Egorova, Anastasiia O. Syrocheva, Alessandro Parodi, Andrey A. Zamyatnin, Fedor A. Kolpakov
Summary: This article introduces the application of nanomedicine in cancer treatment and the role of physiologically based pharmacokinetic modeling in the design and prediction of therapeutic effects of nanocarriers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Daniel Scotcher, Nicola Melillo, Sirisha Tadimalla, Adam S. Darwich, Sabina Ziemian, Kayode Ogungbenro, Gunnar Schuetz, Steven Sourbron, Aleksandra Galetin
Summary: PBPK models were used to explore gadoxetate hepatic transporter kinetics and refine using liver-imaging data, indicating the importance of organ-imaging data for model optimization. The study demonstrated the utility of liver-imaging data in evaluating and refining PBPK transporter IVIVE for quantitative assessment of hepatic drug-drug interactions.
MOLECULAR PHARMACEUTICS
(2021)
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)
