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

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

Publication: Biopharm Drug Dispos
Software: GastroPlus®

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

A population pharmacokinetic and pharmacodynamic analysis of peginesatide in patients with chronic kidney disease on dialysis

Publication: PLoS One

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

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

Publication: J Pharm Sci
Software: GastroPlus®

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.

Application of Target-Mediated Drug Disposition Model to Small Molecule Heat Shock Protein 90 Inhibitors

Application of Target-Mediated Drug Disposition Model to Small Molecule Heat Shock Protein 90 Inhibitors

Publication: Drug Metab Dispos
Software: GastroPlus®

Replacement of hydrogen with fluorine within three pairs of structurally similar small molecule inhibitors of heat shock protein 90 (HSP90) resulted in differences in inhibition constants (K(i)) in vitro as well...

Reduction in Interindividual Variability and Clinical Significance Ratio in Covariate Assessment

Reduction in Interindividual Variability and Clinical Significance Ratio in Covariate Assessment

Conference: ACoP

Covariate analysis has become a customary and expected part of population pharmacokinetic (PK) and pharmacokinetic/ pharmacodynamic (PK/PD) modeling.1 The covariate submodel describes, explains, and…

A Population PK Model for Cariprazine and the Metabolites

A Population PK Model for Cariprazine and the Metabolites

Conference: ACoP

Cariprazine (CAR) is a potent dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors. Cariprazine was originally discovered by Gedeon Richter Plc. in Budapest, Hungary, and is…

Physiologically Based Pharmacokinetic (PBPK) Modeling of Amoxicillin in Neonates and Infants

Physiologically Based Pharmacokinetic (PBPK) Modeling of Amoxicillin in Neonates and Infants

Conference: ACoP
Software: GastroPlus®
Division: PBPK

An amoxicillin PBPK model was previously developed and validated in healthy adults as well as adults with altered renal function [1-2]. The purpose of this study was to explore the utility of the model in...

Single-Dose Safety, Tolerability, and Pharmacokinetics of the Antibiotic GSK1322322, a Novel Peptide Deformylase Inhibitor

Single-Dose Safety, Tolerability, and Pharmacokinetics of the Antibiotic GSK1322322, a Novel Peptide Deformylase Inhibitor

Publication: Antimicrob Agents Chemother
Software: GastroPlus®

GSK1322322 is a potent inhibitor of peptide deformylase, an essential bacterial enzyme required for protein maturation. GSK1322322 is active against community-acquired skin and respiratory...

Interaction of Silymarin Flavonolignans with Organic Anion-Transporting Polypeptides

Interaction of Silymarin Flavonolignans with Organic Anion-Transporting Polypeptides

Publication: Drug Metab Dispos
Software: ADMET Predictor®

Organic anion-transporting polypeptides (OATPs) are multispecific transporters mediating the uptake of endogenous compounds and xenobiotics in tissues that are important for drug...

The Role of Paracellular and Carrier-Mediated Pathways in the Nonlinear Absorption of BCS Class III Substrates for Influx and Efflux Transporters

The Role of Paracellular and Carrier-Mediated Pathways in the Nonlinear Absorption of BCS Class III Substrates for Influx and Efflux Transporters

Conference: BioMed
Division: PBPK

Mechanistic oral absorption simulation of nonlinear dose dependence for BCS Class III transporter substrates is an important objective in preclinical development of NCEs as well as in generic formulation…

Docking and in silico ADMET studies of noraristeromycin, curcumin and its derivatives with Plasmodium falciparum SAH hydrolase: A molecular drug target against malaria

Docking and in silico ADMET studies of noraristeromycin, curcumin and its derivatives with Plasmodium falciparum SAH hydrolase: A molecular drug target against malaria

Publication: Interdiscip Sci
Software: ADMET Predictor®

The Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase (pfSAHH) enzyme has been considered as a potential chemotherapeutic target against malaria due to the amino acid differences...

Computational Exploration of the Role of a Prototypical Damage-Associated Molecular Pattern (DAMP) Molecule in Acetaminophen Hepatotoxicity

Computational Exploration of the Role of a Prototypical Damage-Associated Molecular Pattern (DAMP) Molecule in Acetaminophen Hepatotoxicity

Conference: ISSX
Software: DILIsym®

Drug-induced liver injury (DILI) is a major source of acute liver failure and is one of the leading causes of drug development failures. As such, there remains an important unmet need for earlier...