Drug design is usually understood as “an inventive process of finding new medications based on the knowledge of the biological target” – according to the...
Use of a clinically derived exposure-response relationship to evaluate potential tigecycline-Enterobacteriaceae susceptibility breakpoints
Potential tigecycline-Enterobacteriaceae susceptibility breakpoints were evaluated using 2 approaches, which differed in the nature of the probabilities assessed by MIC value.
Understanding the effect of API properties on bioavailability through absorption modeling
Selection of API phase is one of the first decision points in the formulation development process.
Prediction of Drug Clearance by Glucuronidation from in Vitro Data: Use of Combined Cytochrome P450 and UDP-Glucuronosyltransferase Cofactors in Alamethicin-Activated Human Liver Microsomes
Glucuronidation via UDP-glucuronosyltransferase (UGT) is an increasingly important clearance pathway.
Toward an improved prediction of human in vivo brain penetration
The penetration of drugs into the central nervous system is a composite of both the rate of drug uptake across the blood–brain barrier and the extent of distribution into brain tissue compartments.
Pharmacokinetic/pharmacodynamic modeling and simulation of neutropenia during phase I development of liposome-entrapped paclitaxel
To evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of liposome-entrapped paclitaxel...
Structural Requirements for Drug Inhibition of the Liver Specific Human Organic Cation Transport Protein 1
The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib.
Physicochemical characterization of five glyburide powders: a BCS based approach to predict oral absorption.
The purpose of this study was to investigate the suitability of physicochemical parameters of Active Pharmaceutical Ingredients (APIs) as input functions for the Advanced Compartmental Absorption and Transit Model...
A cellular conformation-based screen for androgen receptor inhibitors
The androgen receptor (AR), a member of the steroid nuclear receptor family of transcription factors, regulates a wide range of physiological...
Physicochemical properties of the nucleoside prodrug R1626 leading to high oral bioavailability
The nucleoside analog R1479 is a potent and highly selective inhibitor of NS5b-directed hepatitis C virus (HCV) RNA polymerase in vitro.
Hepatocellular binding of drugs: correction for unbound fraction in hepatocyte incubations using microsomal binding or drug lipophilicity data
Analogous to the fraction unbound in microsomes (fumic), fraction unbound in hepatocyte incubations (fuhep) is an important parameter in the prediction of intrinsic clearance and potential drug-drug interactions.
Dynamic Dissolution Testing To Establish In Vitro/In Vivo Correlations for Montelukast Sodium, a Poorly Soluble Drug
The objectives of the study was to develop a dissolution test method that can be used to predict the oral absorption of montelukast sodium, and to establish an in vitro/in vivo correlation (IVIVC) using computer simulations.
Applications of Physiologically Based Absorption Models in Drug Discovery and Development
This article describes the use of physiologically based models of intestinal drug absorption to guide the research and development of new drugs.
Pre-clinical pharmacokinetics of UK-453,061, a novel non-nucleoside reverse transcriptase inhibitor (NNRTI), and use of in silico physiologically based prediction tools to predict the oral pharmacokinetics of UK-453,061 in man
UK-453,061 is a novel second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI). Following intravenous bolus administration of UK-453,061 in male rat and infusion administration in dog...
Application of Gastrointestinal Simulation for Extensions for Biowaivers of Highly Permeable Compounds
The goal of this study was to apply gastrointestinal simulation technology and integration of physiological parameters to predict biopharmaceutical drug classification.
The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteers
What is already known about this subject. Vildagliptin is a new, potent, and selective inhibitor of DPP-4. The efficacy and safety of vildagliptin in type 2 diabetes has been...
Drug Lipophilicity and Microsomal Protein Concentration as Determinants in the Prediction of the Fraction Unbound in Microsomal Incubations
The current study was undertaken to elucidate the relative utility of these prediction tools over a range of drug lipophilicity and microsomal protein concentration.
Novel Hierarchical Classification and Visualization Method for Multiobjective Optimization of Drug Properties: Application to Structure-Activity Relationship Analysis of Cytochrome P450 Metabolism
In the lead optimization process, medicinal chemists must consider various chemical properties of active compounds, including ADME/Tox properties, and find the best compromise among these.
A critical evaluation of fasted state simulating gastric fluid (FaSSGF) that contains sodium lauryl sulfate and proposal of a modified recipe.
The aim of this work is to evaluate one of the most commonly used fasted state simulating gastric fluids (FaSSGFs), which contains sodium lauryl sulfate (SLS) (FaSSGFSLS), and propose a more appropriate...