The dependency of metformin in vivo disposition on the rate and extent of dissolution was studied.
Development of a Robust Cytopathic Effect-Based High-Throughput Screening Assay To Identify Novel Inhibitors of Dengue Virus
We have developed a robust cytopathic effect-based high-throughput screening assay to identify inhibitors of dengue virus (DENV) infection.
Parameters for pyrethroid insecticide QSAR and PBPK/PD models for human risk assessment
In this review we have examined the status of parameters required by pyrethroid QSAR-PBPK/PD models for assessing health risks.
Circadian Variations in Exsorptive Transport: In Situ Intestinal Perfusion Data and In Vivo Relevance
The circadian timing system (CTS) governs the 24-h rhythm of the organism and, hence, also main pathways responsible for drug pharmacokinetics.
In Silico Modeling for the Nonlinear Absorption Kinetics of UK-343,664: A P-gp and CYP3A4 Substrate
The aim of this work was to extrapolate in vitro and preclinical animal data to simulate the pharmacokinetic parameters of UK-343,664, a P-glycoprotein (P-gp) and CYP3A4 substrate, in human.
Small-molecule inhibitors of the androgen receptor
The present invention provides a method of inhibiting an androgen receptor by administering a compound of Formula I: or a compound of Formula II: wherein R1, R2, R3 and...
Provisional Biopharmaceutical Classification of Some Common Herbs Used in Western Medicine
The aim of this study was to classify some markers of common herbs used in Western medicine according to the Biopharmaceutical Classification System (BCS).
Lions and tigers and bears, oh my! Three barriers to progress in computer-aided molecular design
The computational chemistry and cheminformatics community faces many challenges to advancing the state of the art.
Effect of gastric pH on the pharmacokinetics of a BCS Class II compound in dogs: Utilization of an artificial stomach and duodenum dissolution model and GastroPlus™ simulations to predict absorption
Dogs are one of the most commonly used non-rodent species in toxicology studies and are known to have basal stomach pH ranging from 2 to 7 in the fasted state.
Application of PBPK modelling in drug discovery and development at Pfizer
Early prediction of human pharmacokinetics (PK) and drug–drug interactions (DDI) in drug discovery and development allows for more informed decision making.
The role of predictive biopharmaceutical modeling and simulation in drug development and regulatory evaluation
Advances in predicting in vivo performance of drug products has the potential to change how drug products are developed and reviewed.
A sequence within the varicella-zoster virus (VZV) OriS is a negative regulator of DNA replication and is bound by a protein complex containing the VZV ORF29 protein
The architecture of the varicella-zoster virus (VZV) origin of DNA replication (OriS) differs significantly from that of the herpes simplex virus (HSV) DNA replication origin.
Development of a physiologically based model for oseltamivir and simulation of pharmacokinetics in neonates and infants
Physiologically based pharmacokinetic (PBPK) modelling can assist in the development of drug therapies and regimens suitable for challenging patient populations such as very young children.
In Vitro and In Silico Strategies to Identify OATP1B1 Inhibitors and Predict Clinical Drug–Drug Interactions
To establish in vitro and in silico models that predict clinical drug–drug interactions (DDIs) with the OATP1B1 (SLCO1B1) transporter.
Selection of oral bioavailability enhancing formulations during drug discovery
The objective of this paper was to identify oral bioavailability enhancing approaches for a poorly water-soluble research compound during drug discovery stages using minimal amounts of material.
Pre-clinical and clinical pharmacokinetics of PF-02413873, a non-steroidal progesterone receptor antagonist
The recently discovered selective nonsteroidal progesterone receptor (PR) antagonist 4-[3-cyclopropyl-1-(methylsulfonylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy-2,6-dimethylbenzonitrile (PF-02413873)...
The Application of Physiologically Based Pharmacokinetic Modelling to Understanding the Clinical Pharmacokinetics of UK-369,003
5-[2-Ethoxy-5-(4-ethyl-piperazine-1-sulfonyl)-pyridin-3-yl]-3-ethyl-2-(2-methoxy-ethyl)-2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (UK-369,003) is a phosphodiesterase-5...
Physiological modeling and assessments of regional drug bioavailability of danoprevir to determine whether a controlled release formulation is feasible
Danoprevir, a potent, selective inhibitor of HCV NS3/4A protease, has a short half-life in humans. Therefore, the feasibility of a controlled release (CR) formulation to allow less frequent dosing...
Simulation of human intravenous and oral pharmacokinetics of 21 diverse compounds using physiologically based pharmacokinetic modelling
The importance of predicting human pharmacokinetics during compound selection has been recognized in the pharmaceutical industry. To this end there are many different approaches that are applied.
A Model of Threshold Behavior Reveals Rescue Mechanisms of Bystander Proteins in Conformational Diseases
Conformational diseases result from the failure of a specific protein to fold into its correct functional state. The misfolded proteins can lead to the toxic aggregation of proteins.