The aim of this study was to evaluate a strategy based on a physiologically based pharmacokinetic (PBPK) model for the prediction of PK profiles in human using in vitro...
Optimizing the Performance of In Silico ADMET General Models According to Local Requirements: MARS Approach. Solubility Estimations As Case Study
The quality of in vitro data used to build in silico absorption, distribution, metabolism, and toxicity (ADMET) models is, in many cases, inconsistent.
In Silico Prediction of Aqueous Solubility: The Solubility Challenge
The dissolution of a chemical into water is a process fundamental to both chemistry and biology. The persistence of a chemical within the environment and the effects of a chemical...
Exposure-response analyses of tigecycline tolerability in healthy subjects
Tigecycline exposure (area under the concentration-time curve [AUC((0-infinity))] and maximum serum concentration [C(max)]) and first occurrence of nausea and vomiting were evaluated in 136 healthy subjects after...
Practical Anticipation of Human Efficacious Doses and Pharmacokinetics Using In Vitro and Preclinical In Vivo Data
Accurate predictions of human pharmacokinetic and pharmacodynamic (PK/PD) profiles are critical in early drug development, as safe, efficacious, and "developable" dosing...
The use of gastrointestinal intubation studies for controlled release development
This review describes clinical results of gastrointestinal intubation studies of eight controlled release (CR) candidates under development during the 1990s and offer
Population pharmacokinetic analysis of linezolid in patients with infectious disease: application to lower body weight and elderly patients
Linezolid (Zyvox), belonging to oxazolidinone antibiotics, is commonly used for the treatment of patients infected with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.
Predicting pKa
One of the most important physicochemical properties of small molecules and macromolecules are the dissociation constants for any weakly acidic or basic groups...
Improving selective androgen receptor modulator discovery and preclinical evaluation
Background: Selective androgen receptor modulators (SARMs) represent a new class of pharmaceuticals that may find wide clinical use. However, selectivity is not understood...
Role of physiological intestinal water in oral absorption
Water volume has impact when the compound has low aqueous solubility. For example, the absorption of compounds with a Biopharmaceutics Classification System...
Prediction of modified release pharmacokinetics and pharmacodynamics from in vitro, immediate release, and intravenous data
The aim of this study was to demonstrate the value of mechanistic simulations in gaining insight into the behaviors of modified release (MR) formulations in vivo and...
Simulations of the nonlinear dose dependence for substrates of influx and efflux transporters in the human intestine
The purpose of this study was to develop simulation and modeling methods for the evaluation of pharmacokinetics when intestinal influx and efflux transporters are involved...
An investigation into the importance of “Very Rapid Dissolution” criteria for drug bioequivalence demonstration using gastrointestinal simulation technology
The Biopharmaceutics Classification System (BCS) is based on the mechanistic assumptions that the rate and extent of oral drug absorption are governed by drug solubility...
Timing and incidence of postoperative infections associated with blood transfusions: analysis of 1,489 orthopedic and cardiac surgery patients
Transfusion rates remain high in cardiac and orthopedic surgery and differ widely across physician practices in spite of growing knowledge that allogeneic...
Computer simulations using GastroPlus to justify a biowaiver for etoricoxib solid oral drug products
The purpose of this study was to compare the dissolution behaviour of etoricoxib in different dissolution media and to establish in vitro/in vivo correlation (IVIVC) using computer simulations.
Non-competitive androgen receptor inhibition in vitro and in vivo
Androgen receptor (AR) inhibitors are used to treat multiple human diseases, including hirsutism, benign prostatic hypertrophy, and prostate cancer, but all available...
Kerfuffle!
To become disheveled. A kerfuffle is the polite term for a cascading series of errors that can be initiated by a seemingly innocuous event that then leads to other...
Predicting pharmacokinetics of drugs using physiologically based modeling – application to food effects
Our knowledge of the major mechanisms underlying the effect of food on drug absorption allows reliable qualitative prediction based on biopharmaceutical properties...
Modelling and PBPK Simulation in Drug Discovery
Physiologically based pharmacokinetic (PBPK) models are composed of a series of differential equations and have been implemented in a number of commercial...
Calculation of molecular lipophilicity: State-of-the-art and comparison of log P methods on more than 96,000 compounds
We first review the state-of-the-art in development of log P prediction approaches falling in two major categories: substructure-based and property-based methods.