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Concentration–Effect Relationships for the Drug of Abuse—γ-hydroxybutyric Acid Blog Post

γ-Hydroxybutyric acid (GHB) is an endogenous neurotransmitter that is abused because of its sedative/hypnotic and euphoric effects. The objectives of this study were to evaluate the concentration-effect relationships of GHB…

What is Pharmacodynamics? Blog Post

Starting with definitions is always helpful… so after defining pharmacokinetics, a definition for pharmacodynamics is in order. The definition of pharmacodynamics (PD) is much less controversial than the definition for…

What is Pharmacokinetics? Blog Post

You might think this is a simple question, especially for an expert in pharmacokinetics. Well, this question is full of controversy with each scientist having their own opinion. I think…

Physiologically-based Mechanistic Modeling to Predict Complex Drug–drug Interactions Involving Simultaneous Competitive and Time-dependent Enzyme Inhibition by Parent Compound and Its Metabolite in Both Liver and Gut—The Effect of Diltiazem on the Time-course of Exposure to Triazolam Blog Post

The aim of this study was to predict the magnitude of metabolic drug-drug interaction (mDDI) between triazolam and diltiazem and its primary metabolite N-desmethyldiltiazem (MA).Relevant in vitro metabolic and inhibitory…

Identification of Cytochrome P450 Isoforms Involved in the Metabolism of Paroxetine and Estimation of Their Importance for Human Paroxetine Metabolism Using a Population-based Simulator Blog Post

We identify here for the first time the low-affinity cytochrome P450 (P450) isoforms that metabolize paroxetine, using cDNA-expressed human P450s measuring substrate depletion and paroxetine-catechol (product) formation by liquid chromatography-tandem…

Under-reporting of Venous and Arterial Thrombotic Events in Randomized Clinical Trials: A Meta-analysis Blog Post

For the detection of unwanted outcomes of new interventions, physicians rely on adverse event reporting. We attempt to quantify the reported incidence of venous thromboembolism (VTE) and arterial thrombosis (AT)…

A Semi-mechanistic Model to Predict the Effects of Liver Cirrhosis on Drug Clearance Blog Post

Liver cirrhosis is characterized by a decrease in functional hepatocytes, lowered circulating levels of plasma proteins and alterations in blood flow due to the development of portacaval shunts. Depending on…

Detection of Lymph Node Metastases by Gadolinium-enhanced Magnetic Resonance Imaging: Systematic Review and Meta-analysis Blog Post

Gadolinium-based contrast agents are used with magnetic resonance imaging (MRI) to highlight tumor vascularity in organs. They are also widely used for primary tumor visualization. We conducted a systematic review…

Population Pharmacokinetics of Teduglutide Following Repeated Subcutaneous Administrations in Healthy Participants and in Patients with Short Bowel Syndrome and Crohn’s Disease Blog Post

Teduglutide is a GLP-2 analog currently evaluated for the treatment of short bowel syndrome, Crohn’s disease, and other gastrointestinal disorders. The population pharmacokinetics (PK) of teduglutide were assessed following daily…

Prediction of Human Drug and Drug Interactions from Time-dependent Inactivation of CYP3A4 in Primary Hepatocytes Using a Population-based Simulator Blog Post

Time-dependent inactivation (TDI) of human cytochromes P450 3A4 (CYP3A4) is a major cause of clinical drug-drug interactions (DDIs). Human liver microsomes (HLM) are commonly used as an enzyme source for…

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