The objective of this study was to assess the impact of observed in vitro dissolution rate differences on in vivo pharmacokinetics for two enteric-coated bead formulations...
The biowaivers extension for BCS Class III drugs: the effect of dissolution rate on on the bioequivalence of BCS Class III IR drugs predicted by computer simulation
The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release...
In Silico Classification of Major Clearance Pathways of Drugs with Their Physiochemical Parameters
Predicting major clearance pathways of drugs is important in understanding their pharmacokinetic properties in clinical use, such as drug-drug interactions and genetic...
Plasma pharmacokinetics of two consecutive doses of ferumoxytol in healthy subjects
Intravenous (IV) iron is used to treat iron-deficiency anemia in patients with chronic kidney disease (CKD). Ferumoxytol is a novel iron formulation administered rapidly as two IV boluses of 510 mg each. In this placebo-controlled, double-blind...
Improving productivity with model-based drug development: an enterprise perspective
The productivity of the pharma enterprise has fallen, as evidenced by a decline in regulatory submissions and less commercial success.
A pH-Dilution Method for Estimation of Biorelevant Drug Solubility along the Gastrointestinal Tract: Application to Physiologically Based Pharmacokinetic Modeling
Physiologically based pharmacokinetic (PBPK) modeling tools have become an integral part of the modern drug discovery−development process.
Rationalizing the development of live attenuated virus vaccines
The design of vaccines against viral disease has evolved considerably over the past 50 years. Live attenuated viruses (LAVs)-those created by passaging a virus in cultured...
AR inhibitors identified by high-throughput microscopy detection of conformational change and subcellular localization
Signaling via the androgen receptor (AR) plays an important role in human health and disease. All currently available anti-androgens prevent ligand access to the receptor...
Quantitative Prediction of Regioselectivity Toward Cytochrome P450/3A4 Using Machine Learning Approaches
In the drug discovery process, it is important to know the properties of both drug candidates and their metabolites.
Prediction of pharmacokinetic profile of valsartan in human based on in vitro uptake transport data
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...