Novel estrogenic therapies are needed that ameliorate menopausal symptoms and have the bone-sparing effects of endogenous estrogens but do not promote breast or...
In Silico Prediction of Ionization
The focus of this chapter is computational methods for the prediction of aqueous ionization of organic molecules.
Population pharmacokinetics of tigecycline in patients with complicated intra-abdominal or skin and skin structure infections
Tigecycline, a first-in-class expanded glycylcycline antimicrobial agent, has demonstrated efficacy in the treatment of complicated skin and skin structure infections...
Biorelevant dissolution media as a predictive tool for glyburide a class II drug
The purpose of this study was to predict the oral absorption of glyburide. Biorelevant dissolution methods, combined with permeability measurements and computational simulations, were used...
In Silico Modeling of Non-Linear Drug Absorption for the P-gp Substrate Talinolol and of Consequences for the Resulting Pharmacodynamic Effect
The aim of the present work was to demonstrate P-glycoprotein's involvement in the non-linear talinolol pharmacokinetics using an advanced compartment and transit model (ACAT) and to compare...
Inhibition of the NF-kappaB pathway by varicella-zoster virus in vitro and in human epidermal cells in vivo
Varicella-zoster virus (VZV) is an alphaherpesvirus that causes varicella and herpes zoster. Using human cellular DNA microarrays, we found that many nuclear factor kappa B...
In silico prediction of aqueous solubility
The fundamentals of aqueous solubility, and the factors that affect it, are briefly outlined, followed by a short introduction to quantitative structure-property relationships.
NIPALSTREE: A New Hierarchical Clustering Approach for Large Compound Libraries and Its Application to Virtual Screening
A hierarchical clustering algorithm NIPALSTREE was developed that is able to analyze large data sets in high-dimensional space. The result can be displayed as a dendrogram.
Mutational analysis of the varicella-zoster virus ORF62/63 intergenic region
The varicella-zoster virus (VZV) ORF62/63 intergenic region was cloned between the Renilla and firefly luciferase genes, which acted as reporters of ORF62 and ORF63...
Pharmacokinetic-pharmacodynamic relationships describing the efficacy of oritavancin in patients with Staphylococcus aureus bacteremia
Bloodstream infections due to antimicrobial-resistant Staphylococcus aureus occur with increasing frequency and represent an important cause of morbidity and mortality.
Are Target-Family-Privileged Substructures Truly Privileged?
One of the early and effective approaches to G-coupled protein receptor target family library design was the analysis of a set of ligands for frequently occurring chemical moieties or substructures.
Assessing the Scaffold Diversity of Screening Libraries
Medicinal chemists have traditionally realized assessments of chemical diversity and subsequent compound acquisition, although a recent study suggests that experts are usually inconsistent in reviewing large data sets.
A strategy for preclinical formulation development using GastroPlus™ as pharmacokinetic simulation tool and a statistical screening design applied to a dog study.
The aim of this paper is to propose a pharmaceutical risk assessment strategy that goes beyond the usual characterisation of a clinical candidate molecule according to the biopharmaceutical classification system (BCS).
Comparison of censored regression and standard regression analyses for modeling relationships between antimicrobial susceptibility and patient- and institution-specific variables
In order to identify patients likely to be infected with resistant bacterial pathogens, analytic methods such as standard regression (SR) may be applied to surveillance data to determine patient- and institution-specific...
Challenges in the transition to model-based development
Practitioners of the art and science of pharmacometrics are well aware of the considerable effort required to successfully complete modeling and simulation activities...
An evaluation of the utility of physiologically based models of pharmacokinetics in early drug discovery
Generic physiologically-based models of pharmacokinetics were evaluated for early drug discovery.
Use of pharmacokinetic-pharmacodynamic target attainment analyses to support phase 2 and 3 dosing strategies for doripenem
A doripenem population pharmacokinetic model and Monte Carlo simulations were utilized for dose regimen decision support for future clinical development.
Viral and cellular gene transcription in fibroblasts infected with small plaque mutants of varicella-zoster virus
Varicella-zoster virus (VZV) is an alphaherpesvirus that causes varicella and herpes zoster. In these experiments, cDNA corresponding to 69 VZV open reading frames was...