During the last decades, the importance of modeling and simulation in clinical drug development, with the goal to qualitatively and quantitatively assess and understand mechanisms of pharmacokinetic processes...
Food Effect in Humans: Predicting the Risk Through In Vitro Dissolution and In Vivo Pharmacokinetic Models
In vitro and in vivo experimental models are frequently used to assess a new chemical entity's (NCE) biopharmaceutical performance risk for food effect (FE) in humans.
Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems
The objective of this study was to develop a level A in vitro-in vivo correlation (IVIVC) for drug-in-adhesive (DIA) type estradiol transdermaldrug delivery systems (TDDS).
Implementing Toxicity Testing in the 21st Century (TT21C): Making safety decisions using toxicity pathways, and progress in a prototype risk assessment
Risk assessment methodologies in toxicology have remained largely unchanged for decades. The default approach uses high dose animal studies, together with human exposure estimates...
Marine Drug Discovery Database (MDDD) – A Database of In silico Predicted Physico-Chemical, Drug Likeness and Toxicological Properties of Marine Compounds
Marine is one of the largest and richest natural resources of bioactive compounds.
Predicting the extent of metabolism using in vitro permeability rate measurements and in silico permeability rate predictions
The Biopharmaceutics Drug Disposition Classification System (BDDCS) can be utilized to predict drug disposition, including interactions with other drugs and transporter or metabolizing enzyme effects based...
An in silico expert system for the identification of eye irritants
This report describes development of an in silico, expert rule-based method for the classification of chemicals into irritants or non-irritants to eye, as defined by the Draize test.
Discovery of a Potent, Orally Available Dual CysLT1 and CysLT2 Antagonist with Dicarboxylic Acid
A potent, orally available dual CysLT1 and CysLT2 receptor antagonist with a dicarboxylic acid is described. 4-(3-(Carboxymethyl)-4-{(E)-2-[4-(4-phenoxybutoxy)phenyl]vinyl}-1H-indol-1-yl)butanoic acid...
Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem
Intraoral (IO) delivery is an alternative administration route to deliver a drug substance via the mouth that provides several advantages over conventional oral dosage forms.
In silico prediction of hERG inhibition
The voltage-gated potassium channel encoded by hERG carries a delayed rectifying potassium current (IKr) underlying repolarization of the cardiac action potential.
Elucidation of the Multiple Activities of Abiraterone by a Synthetic Chemistry Approach
Objective: Novel agents to treat metastatic prostate cancer include a class of drugs which function primarily by inhibiting the action of the CYP17 enzyme, which results...
The importance of critical micellar concentration for the prediction of solubility enhancement in biorelevant media
This study evaluated if the intrinsic surface properties of compounds are related to the solubility enhancement (SE) typically observed in biorelevant media like fasted state simulated intestinal fluids (FaSSIF).
In silico optimization of pharmacokinetic properties and receptor binding affinity simultaneously: a ‘parallel progression approach to drug design’ applied to ß-blockers
The present work exploits the potential of in silico approaches for minimizing attrition of leads in the later stages of drug development.
Phenotypic and molecular characterization of circulating tumor cells (CTCs) in patients with castration resistant prostate cancer (CRPC) undergoing treatment with abiraterone acetate or enzalutamide
Despite the introduction of a number of new treatment options (such as abiraterone acetate and enzalutamide) for castration resistant prostate cancer (CRPC), patients with...
Warfarin-dependent gamma-carboxylation regulates androgen receptor activity
The anti-coagulant warfarin prevents the gamma-carboxylation (gla) of target proteins by interfering with the vitamin K cycle through its inhibition of the vitamin K...
Understanding Disease-Drug Interactions in Cancer Patients: Implications for Dosing Within the Therapeutic Window
The human inflammatory response can result in the alteration of drug clearance through effects on metabolizing enzymes or transporters.
The influence of salt chaotropicity, column hydrophobicity and analytes’ molecular properties on the retention of pramipexole and its impurities
The aim of this study was to examine the interaction of the chaotropic salts of different position in Hofmeister series (CF3COONa, NaClO4, NaPF6) added to the mobile phase with the stationary phases of...
Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model
The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in...
Design, Synthesis and Pharmacological evaluation of N-[4-(4-(alkyl/aryl/heteroaryl) -piperazin-1-yl) -phenyl] -carbamic acid ethyl ester derivatives as novel anticonvulsant agents
A series of alkyl/aryl/heteroaryl piperazine derivatives (37–54) were designed and synthesized as potential anticonvulsant agents. The target compounds are endowed with satisfactory physicochemical as well as pharmacokinetic properties.