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Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone Effects on iNOS mRNA Expression and Nitric Oxide During LPS-induced Inflammation in Rats Blog Post

Increased expression of inducible nitric oxide synthase (iNOS) resulting in nitric oxide elevation represents an important component of inflammatory responses. We assess the effects of methylprednisolone (MPL) on these processes…

Impact of Low-dose Ritonavir on Danoprevir Pharmacokinetics: Results of Computer-based Simulations and a Clinical Drug-drug Interaction Study Blog Post

Danoprevir, a potent, selective inhibitor of the hepatitis C virus (HCV) NS3/4A protease, is metabolized by cytochrome P450 (CYP) 3A. Clinical studies in HCV patients have shown a potential need…

Sex Differences in the Clearance of CYP3A4 Substrates: Exploring Possible Reasons for the Substrate Dependency and Lack of Consensus Blog Post

Sex differences in the clearance of substrates of Cytochrome P4503A (CYP3A4) have been reported frequently although there has been no consensus on reasons for variation in observations amongst drugs which…

Pharmacokinetics, Lymph Node Uptake and Mechanistic PK Model of Near Infrared Dye Labeled Bevacizumab After IV and SC Administration in Mice Blog Post

Our objective was to determine the pharmacokinetics, bioavailability and lymph node uptake of the monoclonal antibodybevacizumab, labeled with the near-infrared (IR) dye 800CW, after intravenous (IV) and subcutaneous (SC) administration…

Prediction of Drug Clearance in a Smoking Population: Modeling the Impact of Variable Cigarette Consumption on the Induction of CYP1A2 Blog Post

The objective of this study was to derive estimates of CYP1A2 abundance as a function of daily cigarette consumption and use these values to predict the clearances of CYP1A2 substrates…

Noninvasive Real-time Fluorescence Imaging of the Lymphatic Uptake of BSA-IRDye 680 Conjugate Administered Subcutaneously in Mice Blog Post

The goal of our studies was to determine lymphatic uptake of bovine serum albumin (BSA) using real-time noninvasive fluorescence imaging. BSA labeled with near-infrared dye (IRDye) 680 was used as…

Modeling and Simulation of Edoxaban Exposure and Response Relationships in Patients with Atrial Fibrillation Blog Post

Edoxaban is a novel, orally available, highly specific direct inhibitor of factor Xa and is currently being developed for the treatment and prevention of venous thromboembolism and prevention of stroke…

Placebo Response Changes Depending on the Neuropathic Pain Syndrome: Results of a Systematic Review and Meta-analysis Blog Post

The purpose of this study was to compare placebo responses in neuropathic pain syndromes through systematic literature review and meta-analysis. We used randomized placebo-controlled trials assessing pain intensity or pain relief…

Screening of Chemicals for Human Bioaccumulative Potential with a Physiologically-based Toxicokinetic Model Blog Post

Human bioaccumulative potential is an important element in the risk assessment of chemicals. Due to the high number of synthetic chemicals, there exists the need to develop prioritisation strategies. The…

Use of a Multistaged Time-dependent Inhibition Assay to Assess the Impact of Intestinal Metabolism on Drug-drug Interaction Potential Blog Post

In early discovery, compounds are often eliminated because of their potential to undergo metabolic activation and/or cytochrome P450 time-dependent inactivation (TDI). The blockbuster drug raloxifene is an example of a…

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