Optimizing the Performance of In Silico ADMET General Models According to Local Requirements: MARS Approach. Solubility Estimations As Case Study

Optimizing the Performance of In Silico ADMET General Models According to Local Requirements: MARS Approach. Solubility Estimations As Case Study

Publication: J Chem Inf Model
Software: ADMET Predictor®

The quality of in vitro data used to build in silico absorption, distribution, metabolism, and toxicity (ADMET) models is, in many cases, inconsistent.

An Uncommon Vignette?

An Uncommon Vignette?

Part 1
The CEO of a pharmaceutical company, tired of late-stage development failures and FDA questioning regarding dose selection, decides to act on the promise of pharmacometrics. “Fix it,” he says to the head of clinical pharmacology, “I don’t care what it takes!” The clinical pharmacologist agrees to take on the challenge and asks for a data programmer and pharmacometrician. Seizing on an opportunity to spearhead an upcoming “end of phase 2” meeting with the FDA, the pharmacologist quickly sketches out his strategy for the modeling activities required for dose selection and justification. He then instructs his programmer to assemble the required dataset using the data from several phase 1 studies and a recently completed phase 2 study. A week later he discovers that the modeling has not begun because the dataset is still not ready. “What is taking so long?” he wonders.

Modeling Fluconazole – a Case with Concentration-Dependent Liver:Plasma Partition Coefficient

Modeling Fluconazole – a Case with Concentration-Dependent Liver:Plasma Partition Coefficient

Conference: AAPS
Division: Simulations Plus

Fluconazole is an antifungal agent widely used in the clinical setting   for the treatment of candidiasis and meningitis. It undergoes minimal metabolism and is excreted renally.

PBPK Modeling of Fluoxetine and its Metabolite Norfluoxetine: Prediction of the Extent of Their Involvement in Drug Interactions

PBPK Modeling of Fluoxetine and its Metabolite Norfluoxetine: Prediction of the Extent of Their Involvement in Drug Interactions

Conference: AAPS
Division: Simulations Plus

The aim of our study was to simulate the human pharmacokinetics of fluoxetine and its major metabolite, norfluoxetine, and predict the magnitude of their drug-drug interactions (DDIs) using physiologically…

In Silico Prediction of Aqueous Solubility: The Solubility Challenge

In Silico Prediction of Aqueous Solubility: The Solubility Challenge

Publication: J Chem Inf Model
Software: ADMET Predictor®

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...

A Pharmacokinetic Simulation-Based Comparison Of Varying Adherence Rates For Paliperidone ER And Risperidone In Patients With Schizophrenia

A Pharmacokinetic Simulation-Based Comparison Of Varying Adherence Rates For Paliperidone ER And Risperidone In Patients With Schizophrenia

Conference: U.S. Psychiatric and Mental Health Congress
Division: Cognigen

Medication adherence is important to successful management of • patients with schizophrenia and related psychotic disorders; patient nonadherence is documented in numerous studies (e.g., 30%-35%…

Square Pegs in Round Holes?

Square Pegs in Round Holes?

A crusading scientist identifies a potential public health threat and uses the internet to get access to a cache of data from several studies. After a quick analysis of the pooled data, he reports a previously unrecognized adverse effect of a widely used drug. Patients and physicians become alarmed, and the drug is pulled from the market. Sound like the plot of a new medical thriller? In fact, a similar scenario has hit the headlines several times in the last 10 years. Each time, controversy about the validity of the analysis and conclusions was loud and lasting.

Simulation of Cilostazol Absorption and Pharmacokinetics

Simulation of Cilostazol Absorption and Pharmacokinetics

Conference: ISSX
Division: Simulations Plus

Cilostazol absorption and pharmacokinetics were simulated using GastroPlus™. The program’s Advanced Compartmental and Transit (ACAT) model described the absorption of the drug, while pharmacokinetics was…

Physiologically Based Model for Ketoconazole Disposition and Prediction of its Drug-Drug Interactions

Physiologically Based Model for Ketoconazole Disposition and Prediction of its Drug-Drug Interactions

Conference: ISSX
Division: Simulations Plus

Ketoconazole is a potent inhibitor of the major drug-metabolizing enzyme, CYP3A4 and, as the result of that, is involved in many drug-drug interactions.  Pharmacokinetic (PK) information available for…

Forensic Pharmacometrics: Part 1 – Data Assembly

Forensic Pharmacometrics: Part 1 – Data Assembly

Conference: ACoP
Division: Cognigen

Pharmacometric modeling and simulation (M&S) is moving from merely describing pharmacokinetic (PK) and pharmacodynamic (PD) phenomena to informing critical drug development and regulatory decision-making…

Exposure-response analyses of tigecycline tolerability in healthy subjects

Exposure-response analyses of tigecycline tolerability in healthy subjects

Publication: Diagn Microbiol.Infect.Dis
Division: Cognigen

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

Practical Anticipation of Human Efficacious Doses and Pharmacokinetics Using In Vitro and Preclinical In Vivo Data

Publication: AAPS J
Software: GastroPlus®

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

The use of gastrointestinal intubation studies for controlled release development

Authors: Sutton SC
Publication: Br J Clin Pharmacol
Software: GastroPlus®

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

Population pharmacokinetic analysis of linezolid in patients with infectious disease: application to lower body weight and elderly patients

Publication: J Clin Pharmacol
Division: Cognigen

Linezolid (Zyvox), belonging to oxazolidinone antibiotics, is commonly used for the treatment of patients infected with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.