Semi-mechanistic PK/PD Model of the Effect of Odanacatib, a Cathepsin K Inhibitor, on Bone Turnover to Characterize Lumbar Spine Bone Mineral Density in Two Phase II Studies of Postmenopausal Women

Semi-mechanistic PK/PD Model of the Effect of Odanacatib, a Cathepsin K Inhibitor, on Bone Turnover to Characterize Lumbar Spine Bone Mineral Density in Two Phase II Studies of Postmenopausal Women

Authors: Zajic S, Stone J, Jaworowicz DJ, Leung A, Duong LT, Passarell JA, Fiedler-Kelly J, Cohn D, Verbruggen N, Stoch A
Keywords: Odanacatib, PK/PD, PopPK, population pharmacokinetics
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Odanacatib (MK-0822), a potent, orally-active inhibitor of cathepsin K, is under clinical development for treatment of postmenopausal osteoporosis. This poster describes base model development of a...

Development of a Physiologically Based Pharmacokinetic (PBPK) Model for Predicting Deposition and Disposition follo · g Inhaled and Intranasal Administration

Development of a Physiologically Based Pharmacokinetic (PBPK) Model for Predicting Deposition and Disposition follo · g Inhaled and Intranasal Administration

Authors: Miller NA, Chaudhuri S, Lukacova V, Damian-Iordache V, Bayliss MK, Woltosz WS
Keywords: inhaled drug, intranasal drug, PBPK modeling, pharmacokinetic, plasma concentration, pulmonary, pulmonary playlist
Software: GastroPlus®
Division: PBPK

The selection of a biologically active molecule as a successful inhaled therapeutic agent depends on its pharmacokinetic and safety properties...

Modeling Drug Disposition of Timolol in Ocular Tissues of Rabbit following Topical Eye Drops

Modeling Drug Disposition of Timolol in Ocular Tissues of Rabbit following Topical Eye Drops

Authors: Chaudhuri S, Lukacova V, Woltosz WS
Conference: ISOPT
Keywords: clonidine, ocular, PBPK, rabbit, timolol
Software: GastroPlus®
Division: PBPK

Recently, we reported the successful application of a novel mathematical model describing drug disposition in eye compartments to simulate disposition of clonidine  after topical (eye drop) administration.

Prediction of pharmacokinetic profile of valsartan in human based on in vitro uptake transport data

Prediction of pharmacokinetic profile of valsartan in human based on in vitro uptake transport data

Authors: Poirier A, Cascais AC, Funk C, Lavé T
Publication: J Pharmacokinet Pharmacodyn
Keywords: administration and dosage, biological models, drug interaction, metabolism, oral administration, pharmacokinetics, rats
Software: GastroPlus®

The aim of this study was to evaluate a strategy based on a physiologically based pharmacokinetic (PBPK) model for the prediction of PK profiles in human using in vitro...

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

Authors: Oyarzabal J, Pastor J, Howe TJ
Publication: J Chem Inf Model
Keywords: ADME/Tox properties, in silico absorption, in vitro, predictive models
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.

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

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

Authors: Fraczkiewicz G, Parrott N, Lukacova V, Bolger MB, Crison JR, Woltosz WS, Lavé T
Conference: AAPS
Keywords: ADMET, antifungal, candidiasis, fluconazole, meningitis, PBPK
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

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

Authors: Fraczkiewicz G, Lukacova V, Parrott N, Bolger MB, Crison JR, Woltosz WS, Lavé T
Conference: AAPS
Keywords: ADMET, Cp-Time, DDIs, drug-drug interactions (DDIs), fluoxetine, norfluoxetine, PBPK, tissue:plasma
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

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

Authors: Hewitt M, Cronin MT, Enoch SJ, Madden JC, Roberts DW, Dearden JC
Publication: J Chem Inf Model
Keywords: aqueous solubility, dissolution, in silico models, solubility
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

Authors: DeVane CL, Passarell JA, Fiedler-Kelly J, Ludwig E, Martinez L, Canuso CM
Conference: U.S. Psychiatric and Mental Health Congress
Keywords: compliance, dopamine, dosage regimen, Phase 1, Phase 3, psychiatry, psychotherapeutic agents, steady state, target bounds, two-compartment model, virtual
Division: Clinical Pharmacology and Pharmacometrics (CPP)

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%…