Barefoot Kahn (hawksteel70)
Pharmacokinetic-pharmacodynamic model is a kind of language that quantitatively describes the drug-related outcomes in the form of mathematical formula. Various outcomes can be subjected to modeling analysis if they can be expressed in numbers. Empirical models have been widely and successfully applied in drug development and research. MSA-2 molecular weight However, a more competitive drug development environment requires more accurate and predictive models in the early stages of drug development. Accordingly, the subjects of PK-PD modeling have been extended from clinical data to preclinical and in vitro data in the discovery stage. More mechanistic and predictive models, such as physiologically based pharmacokinetic and quantitative system-based pharmacology models, are being increasingly used owing to the growing need to characterize drugs more accurately at the earliest. This tutorial briefly introduces the essential concepts of PK-PD modeling and simulation and describes the recent changing roles of PK-PD model for application in novel drug development process. Copyright © 2019 Hyeong-Seok Lim.In 2005, the International Council for Harmonization (ICH) established cardiotoxicity assessment guidelines to identify the risk of Torsade de Pointes (TdP). It is focused on the blockade of the human ether-à-go-go-related gene (hERG) channel known to cause QT/QTc prolongation and the QT/QTc prolongation shown on the electrocardiogram. However, these biomarkers are not the direct risks of TdP with low specificity as the action potential is influenced by multiple channels along with the hERG channel. Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative emerged to address limitations of the current model. The objective of CiPA is to develop a standardized in silico model of a human ventricular cell to quantitively evaluate the cardiac response for the cardiac toxicity risk and to come up with a metric for the TdP risk assessment. In silico working group under CiPA developed a standardized and reliable in silico model and a metric that can quantitatively evaluate cellular cardiac electrophysiologic activity. The implementation mainly consists of hERG fitting, Hill fitting, and action potential simulation. In this review, we explained how the in silico model of CiPA works, and briefly summarized current overall CiPA studies. We hope this review helps clinical pharmacologists to understand the underlying estimation process of CiPA in silico modeling. Copyright © 2019 Min-Gul Kim.Digital therapeutics (DTx) is a new subsection of digital health that is primarily driven by software and will be of great interest to clinical pharmacologists. In this article, an overview of DTx, including definition, position in the landscape of therapeutics, product categories, benefits, and challenges, is provided. Discussions from the point of view of clinical pharmacology are presented, as DTx should have exposure-response relationships. The principles of clinical pharmacology can be applied to DTx as they are comparable to pharmacotherapy. Clinical pharmacology has great potential in the development, application, and regulation of DTx. Copyright © 2019 Jae-Yong Chung.Background Toxoplasma gondii (T. gondii) is a protozoan parasite that infects a wide range of warm-blooded animals and humans. The conventional anti-Toxoplasma treatments cause significant toxicity. Brassicaceae family contains several medicinal plants with anti-inflammatory, chemopreventive, insecticide, antibacterial, antiviral, and antiparasitic effects. In this study, the hydroalcoholic extract of some Brassicaceae species was investigated against T. gondii in vitro. Materials and Methods Seeds of Alyssum homolocarpum, Lepidium perfoliatum, Lepidium sativum, and aerial parts of Nasturtium officinale and Capsella bursa-pastoris were extracted by maceration method using 80% ethanol. Vero cells were treated with different concentrations (5-600 μg/mL) of the extracts and pyrimeth