Development of A Mechanistic in vitro – in vivo Correlation for Theophylline

Development of A Mechanistic in vitro – in vivo Correlation for Theophylline

Authors: Chung J, Lukacova V, Bolger MB, Woltosz WS
Conference: AAPS
Keywords: ACAT model, Advanced Compartmental Absorption and Transit (ACAT™) model, In vitro in vivo correlations (IVIVC), intravenous, IVIVC, lung diseases, PBPK, Theophylline
Software: GastroPlus®
Division: PBPK

Theophylline is used to prevent and treat wheezing, shortness of breath, and difficulty breathing caused by asthma, chronic bronchitis, emphesema, and other lung diseases. Immediate release oral…

Application of a Respiratory PBPK Model for Predicting Deposition and Disposition following Inhaled Administration of Morphine

Application of a Respiratory PBPK Model for Predicting Deposition and Disposition following Inhaled Administration of Morphine

Authors: Chaudhuri S, Lukacova V, Woltosz WS
Conference: AAPS
Keywords: ACAT, additional dosage routes, Advanced Compartmental Absorption and Transit (ACAT™) model, inhaled, PBPK, pulmonary
Software: GastroPlus®
Division: PBPK

Demonstrate the pulmonary component of the GastroPlus™ Additional Dosage Routes Module™ (ADRM) simulation to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model for inhaled…

Mechanistic PBPK Simulation in Place of In Vivo Drug-Drug Interaction (DDI) Studies for Compliance with Regulatory Requirements of EMA and FDA

Mechanistic PBPK Simulation in Place of In Vivo Drug-Drug Interaction (DDI) Studies for Compliance with Regulatory Requirements of EMA and FDA

Authors: Bolger MB, Woltosz WS, Lukacova V, Chung J, Zhou H, Fraczkiewicz G, Lavé T, Parrott N
Conference: AAPS
Keywords: DDIs, drug-drug interactions (DDIs), European Medicines Agency (EMA), PBPK, PBPK modeling, U.S. FDA
Software: GastroPlus®
Division: PBPK

To highlight the application and validation of PBPK DDI simulation results obtained using GastroPlus™ in compliance with newly proposed European Medicines Agency (EMA) and US FDA guidelines for the…

Bendamustine pharmacokinetic profile and exposure-response relationships in patients with indolent non-Hodgkin’s lymphoma

Bendamustine pharmacokinetic profile and exposure-response relationships in patients with indolent non-Hodgkin’s lymphoma

Authors: Owen JS, Melhem M, Passarell JA, D’Andrea D, Darwish M, Kahl B
Publication: Cancer Chemother Pharmacol
Keywords: alkylating agent, body surface area, BSA, cancer, dose proportionality, drug-resistant cancer, intravenous, IV, metabolites, NONMEM, PK
Division: Clinical Pharmacology and Pharmacometrics (CPP)

The pharmacokinetic profiles of bendamustine and active metabolites were defined in patients with rituximab-refractory, relapsed indolent B-cell non-Hodgkin's lymphoma, and supported understanding of exposure-response relationships for efficacy and safety.

Dissolution modeling of bead formulations and predictions of bioequivalence for a highly soluble, highly permeable drug

Dissolution modeling of bead formulations and predictions of bioequivalence for a highly soluble, highly permeable drug

Authors: Sperry DC, Thomas SJ, Lobo E
Publication: Mol Pharm
Keywords: chemistry, dissolution, equivalency, humans, in vitro, in vivo, intestinal absorption, permeability, pharmaceutical chemistry, pharmacokinetics, solubility, therapeutic
Software: GastroPlus®

The objective of this study was to assess the impact of observed in vitro dissolution rate differences on in vivo pharmacokinetics for two enteric-coated bead formulations...

Beyond Filters: ADMET Risk™ for Multi-objective Drug Development

Beyond Filters: ADMET Risk™ for Multi-objective Drug Development

Authors: Zhang J, Clark RD, Fraczkiewicz R, Waldman M, Woltosz WS, Bolger MB
Conference: ACS
Keywords: absorption distribution metabolism and excretion (ADME), ADMET-risk, drug development
Software: ADMET Predictor®
Division: PBPK

We calculated predictions for over 30 properties relevant to absorption, distribution, metabolism, excretion and toxicity (ADMET) for a large and pharmaceutically pertinent...

The biowaivers extension for BCS Class III drugs: the effect of dissolution rate on on the bioequivalence of BCS Class III IR drugs predicted by computer simulation

The biowaivers extension for BCS Class III drugs: the effect of dissolution rate on on the bioequivalence of BCS Class III IR drugs predicted by computer simulation

Authors: Tsume Y, Amidon GL
Publication: Mol Pharm
Keywords: Amoxicillin, cell membrane, computer simulation, gastric emptying, gastrointestinal tract (GIT), humans, metabolism, permeability, pharmaceutical preparations, Propranolol
Software: GastroPlus®

The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release...

In Silico Classification of Major Clearance Pathways of Drugs with Their Physiochemical Parameters

In Silico Classification of Major Clearance Pathways of Drugs with Their Physiochemical Parameters

Authors: Kusama M, Toshimoto K, Maeda K, Hirai Y, Imai S, Chiba K, Akiyama Y, Sugiyama Y
Publication: Drug Metab Dispos
Keywords: clearance, hepatic uptake, in silico, pharmacokinetics, pharmacological/toxicological effects
Software: ADMET Predictor®

Predicting major clearance pathways of drugs is important in understanding their pharmacokinetic properties in clinical use, such as drug-drug interactions and genetic...

Plasma pharmacokinetics of two consecutive doses of ferumoxytol in healthy subjects

Plasma pharmacokinetics of two consecutive doses of ferumoxytol in healthy subjects

Authors: Pai AB, Nielsen JC, Kausz A, Miller P, Owen JS
Publication: Clin Pharmacol Ther
Keywords: erythropoiesis, hemoglobin
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Intravenous (IV) iron is used to treat iron-deficiency anemia in patients with chronic kidney disease (CKD). Ferumoxytol is a novel iron formulation administered rapidly as two IV boluses of 510 mg each. In this placebo-controlled, double-blind...

Improving productivity with model-based drug development: an enterprise perspective

Improving productivity with model-based drug development: an enterprise perspective

Authors: Grasela TH, Slusser R
Publication: Clin Pharmacol Ther
Keywords: cost, critical path initiative, decision, design review, disease-drug, drug-disease, empirical, FDA, governance, infrastructure, knowledge gap, life cycle, M&S, management, R&D, regulatory, research and development, risk, simulation
Division: Clinical Pharmacology and Pharmacometrics (CPP)

The productivity of the pharma enterprise has fallen, as evidenced by a decline in regulatory submissions and less commercial success.

A pH-Dilution Method for Estimation of Biorelevant Drug Solubility along the Gastrointestinal Tract: Application to Physiologically Based Pharmacokinetic Modeling

A pH-Dilution Method for Estimation of Biorelevant Drug Solubility along the Gastrointestinal Tract: Application to Physiologically Based Pharmacokinetic Modeling

Authors: Gao Y, Carr RA, Spence JK, Wang WW, Turner TM, Lipari JM, Miller JM
Publication: Mol Pharm
Keywords: amorphous solid dispersions, biorelevant dissolution, Physiologically based pharmacokinetic (PBPK) modeling, solubility enabling formulations
Software: GastroPlus®

Physiologically based pharmacokinetic (PBPK) modeling tools have become an integral part of the modern drug discovery−development process.