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.
Application of patient population-derived pharmacokinetic-pharmacodynamic relationships to tigecycline breakpoint determination for staphylococci and streptococci
Correctly determined susceptibility breakpoints are important to both the individual patient and to society at large. A previously derived patient population...
Toward an In Vivo Dissolution Methodology: A Comparison of Phosphate and Bicarbonate Buffers
The purpose of this research was to evaluate the difference between the pharmaceutical phosphate buffers and the gastrointestinal bicarbonates in dissolution of ketoprofen and indomethacin...
Justification of biowaiver for carbamazepine, a low soluble high permeable compound, in solid dosage forms based on IVIVC and gastrointestinal simulation
The aim of the present study was to use gastrointestinal simulation technology and in vitro-in vivo correlation (IVIVC) as tools to investigate a possible extension of biowaiver criteria...
Analysis of Risk Factors in Human Bioequivalence Study That Incur Bioinequivalence of Oral Drug Products
In the study of human bioequivalence (BE), newly developed oral products sometimes fail to prove BE with a reference product due to the high variability in pharmacokinetic (PK)...
Busting the Black Box Myth: Designing Out Unwanted ADMET Properties with Machine Learning Approaches
Drug design is usually understood as “an inventive process of finding new medications based on the knowledge of the biological target” – according to the...
Use of a clinically derived exposure-response relationship to evaluate potential tigecycline-Enterobacteriaceae susceptibility breakpoints
Potential tigecycline-Enterobacteriaceae susceptibility breakpoints were evaluated using 2 approaches, which differed in the nature of the probabilities assessed by MIC value.
Understanding the effect of API properties on bioavailability through absorption modeling
Selection of API phase is one of the first decision points in the formulation development process.
Prediction of Drug Clearance by Glucuronidation from in Vitro Data: Use of Combined Cytochrome P450 and UDP-Glucuronosyltransferase Cofactors in Alamethicin-Activated Human Liver Microsomes
Glucuronidation via UDP-glucuronosyltransferase (UGT) is an increasingly important clearance pathway.
Toward an improved prediction of human in vivo brain penetration
The penetration of drugs into the central nervous system is a composite of both the rate of drug uptake across the blood–brain barrier and the extent of distribution into brain tissue compartments.
Pharmacokinetic/pharmacodynamic modeling and simulation of neutropenia during phase I development of liposome-entrapped paclitaxel
To evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of liposome-entrapped paclitaxel...
Structural Requirements for Drug Inhibition of the Liver Specific Human Organic Cation Transport Protein 1
The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib.