Using a dataset with more than 6000 compounds, the performance of eight quantitative structure activity relationships (QSAR) models was evaluated: ACD/Tox Suite, Absorption, Distribution...
A Simplified PBPK Modeling Approach for Prediction of Pharmacokinetics of Four Primarily Renally Excreted and CYP3A Metabolized Compounds During Pregnancy
During pregnancy, a drug's pharmacokinetics may be altered and hence anticipation of potential systemic exposure changes is highly desirable.
Incorporation of Physiologically Based Pharmacokinetic Modeling in the Evaluation of Solubility Requirements for the Salt Selection Process: A Case Study Using Phenytoin
In the pharmaceutical industry, salt is commonly used to improve the oral bioavailability of poorly soluble compounds. Currently, there is a limited understanding on the solubility...
Validation of quantitative structure–activity relationship models to predict water-solubility of organic compounds
Water-solubility is an important physicochemical property in pharmaceutical and environmental studies. We assessed the performance of five predictive computer models: ACD/PhysChem History...
Is the full potential of the Biopharmaceutics Classification System reached?
In this paper we analyse how the biopharmaceutics classification system (BCS) has been used to date. A survey of the literature resulted in a compilation of 242 compounds for which BCS classes were reported.
Bioisosteric approach in designing new monastrol derivatives: an investigation on their ADMET prediction using in silico derived parameters
Medicinal chemists are facing an increasing challenge to deliver safer and more effective medicines. An appropriate balance between drug-like properties such as solubility, permeability, metabolic stability...
Profiling Biopharmaceutical Deciding Properties of Absorption of Lansoprazole Enteric-Coated Tablets Using Gastrointestinal Simulation Technology
The aim of the present study was to correlate in vitro properties of drug formulation to its in vivo performance, and to elucidate the deciding properties of oral absorption.
Utility of Physiologically Based Modeling and Preclinical In Vitro/In Vivo Data to Mitigate Positive Food Effect in a BCS Class 2 Compound
Physiologically based pharmacokinetic (PBPK) modeling has become a useful tool to estimate the performance of orally administrated drugs.
Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery
Poor water-solubility is a common characteristic of drug candidates in pharmaceutical development pipelines today. Various processes have been developed to increase the solubility, dissolution rate...
Oral delivery of anticancer drugs: Challenges and opportunities
The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes...
In Vitro-In Vivo Correlation of Efavirenz Tablets Using GastroPlus®
The aim of the present work was to use GastroPlus™ software for the prediction of pharmacokinetic profiles and in vitro-in vivo correlation (IVIVC) as tools to optimize the development of new generic medications.
Physiologically Based Pharmacokinetic Modelling to Predict Single- and Multiple-Dose Human Pharmacokinetics of Bitopertin
This paper describes the use of physiologically based pharmacokinetic (PBPK) modelling and preclinical data to gain insights into and predict bitopertin clinical pharmacokinetics.
In Vitro Characterization of Axitinib Interactions with Human Efflux and Hepatic Uptake Transporters: Implications for Disposition and Drug Interactions
Axitinib is an inhibitor of tyrosine kinase vascular endothelin growth factor receptors 1, 2, and 3. The ATP-binding cassette (ABC) and solute carrier (SLC) transport properties of axitinib...
Investigation of clinical pharmacokinetic variability of an opioid antagonist through physiologically based absorption modeling
Identifying the source of inter- and/or intrasubject variability in pharmacokinetics (PK) provides fundamental information in understanding the pharmacokinetics-pharmacodynamics relationship...
Dendritic Cell Immunoreceptor Is a New Target for Anti-AIDS Drug Development: Identification of DCIR/HIV-1 Inhibitors
The HIV-1 pandemic continues to expand while no effective vaccine or cure is yet available. Existing therapies have managed to limit mortality and control viral proliferation, but are associated with side effects...
Similarity-based virtual screening for microtubule stabilizers reveals novel antimitotic scaffold
Microtubules are among the most studied and best characterized cancer targets identified to date. Many microtubule stabilizers have been introduced so far that work by disrupting the...
Low systemic testosterone levels induce androgen maintenance in benign rat prostate tissue
Prostate cancer (PC) is both an age- and an androgen-dependent disease. Paradoxically, systemic levels of androgens decline with age as the risk of PC rises. While there is no...
Physiologically based pharmacokinetic and pharmacodynamic modeling of an antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in a mouse xenograft model of human breast cancer
The inhibitors of apoptosis proteins (IAPs) are a class of key apoptosis regulators overexpressed or dysregulated in cancer. SM-406/AT-406 is a potent and selective small molecule mimetic of...
A population pharmacokinetic and pharmacodynamic analysis of peginesatide in patients with chronic kidney disease on dialysis
Peginesatide (OMONTYS®) is an erythropoiesis-stimulating agent that was indicated in the United States for the treatment of anemia due to chronic kidney disease in adult patients on dialysis prior to...
Compartmental absorption modeling and site of absorption studies to determine feasibility of an extended-release formulation of an HIV-1 attachment inhibitor phosphate ester prodrug
BMS-663068 is a phosphonooxymethyl ester prodrug under development for the treatment of HIV/AIDS. The prodrug is designed to overcome the solubility-limited bioavailability of the active moiety, BMS-626529.