BACKGROUND Evaluating the potential risk of metabolic drug-drug interactions (DDIs) is clinically important. OBJECTIVE To develop a physiologically based pharmacokinetic (PBPK) model for sarpogrelate hydrochloride and its active metabolite, (R,S)-1-{2-[2-(3-methoxyphenyl)ethyl]-phenoxy}-3-(dimethylamino)-2-propanol (M-1), in order to predict DDIs between sarpogrelate and the clinically releva...

It is no coincidence that the reports of two meetings, one organized by the US Food and Drug Administration (FDA), in March 2014, and the other by the UK Medicines and Healthcare Products Regulatory (MHRA), in collaboration with ABPI (the Association of British Pharmaceutical Industry), in June 2014, have been published in tandem in CPT-PSP.12 Both reports deal with the same topic, namely, the ...

The inhibitors of apoptosis proteins (IAPs) are a class of key apoptosis regulators overexpressed or dysregulated in cancer. SM-406/AT-406 is a potent and selective small molecule mimetic of Smac that antagonizes the inhibitor of apoptosis proteins (IAPs). A physiologically based pharmacokinetic and pharmacodynamic (PBPK-PD) model was developed to predict the tissue concentration-time profiles ...

Glycyrrhizin (GL) is a widely used food additive which can cause severe pseudoaldosteronism at high doses or after a long period of consumption. The aim of the present study was to develop a physiologically based pharmacokinetic (PBPK) pharmacodynamic (PD) model for GL-induced pseudoaldosteronism to improve the safe use of GL. Since the major metabolite of GL, glycyrrhetic acid (GA), is largely...

Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment, but previous in vivo validation was conducted only in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five vo...

Clopidogrel is a prodrug that needs to be converted to its active metabolite (clopi-H4) in two sequential cytochrome P450 (P450)dependent steps. In the present study, a dynamic physiologically based pharmacokinetic (PBPK) model was developed in Simcyp for clopidogrel and clopi-H4 using a specific sequential metabolite module in four populations with phenotypically different CYP2C19 activity (po...

Clopidogrel is a prodrug that needs to be converted to its active metabolite (clopi-H4) in two sequential cytochrome P450 (P450)-dependent steps. In the present study, a dynamic physiologically based pharmacokinetic (PBPK) model was developed in Simcyp for clopidogrel and clopi-H4 using a specific sequential metabolite module in four populations with phenotypically different CYP2C19 activity (p...

Here we describe a toolkit for presenting physiologically based pharmacokinetic (PBPK) models in modular graphical view the BioUML platform. Firstly, demonstrate capabilities PBPK modeling tested on an existing model of nanoparticles delivery to solid tumors mice. Secondly, provide guidance conversion code from text language like Berkeley Madonna visual diagram BioUML. We give step-by-step expl...

A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was developed to simulate the concentration and effects of low-level chemical warfare agents (CWA) in the Göttingen minipig. The model code was written to account for absorption of CWAs from multiple sites (respiratory tract – lower and upper, dermal, ocular) after vapor exposure. Literature references to minipig physiology...

Introduction: In vitro and earlier animal studies implicated altered metabolism of caffeine as a probe for CYP1A2 enzyme activity in diabetic disease state. However clinical studies in humans reported controversial findings. This study is aimed to compare the differences in the metabolism of caffeine in Non-Insulin Dependent Diabetes Mellitus (NIDDM) patients and in healthy subjects by using Ph...