In vitro--in vivo correlations (IVIVC) are generally accepted as a valuable tool in modified release formulation development aimed at (i) quantifying the in vivo drug delivery profile and...
The acute effects of daily nicotine intake on heart rate – A toxicokinetic and toxicodynamic modelling study
Joint physiologically-based toxicokinetic and toxicodynamic (PBTK/TD) modelling was applied to simulate concentration-time profiles of nicotine, a well-known stimulant, in the human body following single and repeated dosing.
Pharmacokinetics of Paracetamol in Göttingen Minipigs: In Vivo Studies and Modeling to Elucidate Physiological Determinants of Absorption
Onset and rate of gastric emptying are important determinants of drug absorption after oral dosing.
Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification
Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate.
Detection and phenotyping of circulating tumor cells in high-risk localized prostate cancer
Background: In this study, we aimed to determine the feasibility of identifying CTCs in patients with HRLPC, using a modified isolation procedure using the CellSearch...
Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: A comparison with carbamazepine, oxcarbazepine and lacosamide
This study aimed at evaluating the effects of eslicarbazepine, carbamazepine (CBZ), oxcarbazepine (OXC) and lacosamide (LCM) on the fast and slow inactivated states of voltage-gated sodium channels (VGSC).
Computational Predictions of Glass-Forming Ability and Crystallization Tendency of Drug Molecules
Amorphization is an attractive formulation technique for drugs suffering from poor aqueous solubility as a result of their high lattice energy.
RNA-seq reveals aurora kinase-driven mTOR pathway activation in patients with sarcomatoid metastatic renal cell carcinoma
Sarcomatoid metastatic renal cell carcinoma (mRCC) is associated with a poor prognosis, and the biology of the disease has been inadequately characterized.
Physiologically Based Absorption Modelling to Predict the Impact of Drug Properties on Pharmacokinetics of Bitopertin
Bitopertin (RG1678) is a glycine reuptake inhibitor in phase 3 trials for treatment of schizophrenia. Its clinical oral pharmacokinetics is sensitive to changes in drug substance particle size and dosage form.
Discovery of furan-2-carbohydrazides as orally active glucagon receptor antagonists
Furan-2-carbohydrazides were found as orally active glucagon receptor antagonists. Starting from the hit compound 5, we successfully determined the structure activity relationships of a series...
Network representations and methods for the analysis of chemical and biochemical pathways
Systems biologists increasingly use network representations to investigate biochemical pathways and their dynamic behaviours.
In Silico Prediction of Major Drug Clearance Pathways by Support Vector Machines with Feature-Selected Descriptors
We have previously established an in silico classification method ("CPathPred") to predict the major clearance pathways of drugs based on an empirical decision with only four physicochemical...
Dissolution testing combined with computer simulation technology to evaluate the bioequivalence of domestic amoxicillin capsule
Re-evaluation of bioequivalence of generic drugs is one of the key research focus currently. As a means to ensure consistency of the therapeutic effectiveness of drug products, clinical bioequivalence...
Intestinal transport of TRH analogs through PepT1: the role of in silico and in vitro modeling
The present study involves molecular docking, molecular dynamics (MD) simulation studies, and Caco-2 cell monolayer permeability assay to investigate the effect of structural modifications on...
Enhanced Solubility and Oral Bioavailability of y-Tocotrienol Using a Self-Emulsifying Drug Delivery System (SEDDS)
The aim of this study was to evaluate the in vitro and in vivo performance of γ-tocotrienol (γ-T3) incorporated in a self-emulsifying drugdelivery system (SEDDS)...
Design of a General-Purpose European Compound Screening Library for EU-OPENSCREEN
This work describes a collaborative effort to define and apply a protocol for the rational selection of a general-purpose screening library, to be used by the screening platforms affiliated with the EU-OPENSCREEN initiative.
Predicting when Biliary Excretion of Parent Drug is a Major Route of Elimination in Humans
Biliary excretion is an important route of elimination for many drugs, yet measuring the extent of biliary elimination is difficult, invasive, and variable.
Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid-Mediated DILI
Bile salt export pump (BSEP) inhibition has been proposed to be an important mechanism for drug-induced liver injury (DILI).
Maximum Entropy in Drug Discovery
Drug discovery applies multidisciplinary approaches either experimentally, computationally or both ways to identify lead compounds to treat various diseases.
Physiologically based pharmacokinetic modeling for assessing the clinical drug-drug interaction of alisporivir
Alisporivir is a novel cyclophilin-binding molecule with potent anti-hepatitis C virus (HCV) activity. In vitro data from human liver microsomes suggest that alisporivir is a substrate and a time-dependent inhibitor (TDI) of CYP3A4.