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.

Forensic Pharmacometrics: Part 2 – Deliverables for Regulatory Submission

Forensic Pharmacometrics: Part 2 – Deliverables for Regulatory Submission

Authors: Grasela TH, Fiedler-Kelly J, Ludwig E, Passarell JA, Hitchcock D
Conference: PAGE
Keywords: analysis-ready, assessment, compliance, critical path, data analysis plan, data assembly, dataset, decision-making, deliverables, documentation, drug development process, due diligence, EMEA. FDA, final technical reports, forensic pharmacometrics, gap analysis, NONMEM, PK/PD methodology, quality assurance, regulatory, standards, strategic, validation
Division: Clinical Pharmacology and Pharmacometrics (CPP)

As modeling and simulation results become increasingly integral to critical development-related decision-making and program outcomes, the consequences of poor documentation of pharmacometric analyses can…

Physiologically-Based Pharmacokinetic (PBPK) Modeling of Diltiazem-Midazolam Drug-Drug Interaction (DDI)

Physiologically-Based Pharmacokinetic (PBPK) Modeling of Diltiazem-Midazolam Drug-Drug Interaction (DDI)

Authors: Lukacova V, Bolger MB, Woltosz WS
Conference: DDI
Keywords: ACAT model, ADMET, DDIs, drug-drug interactions (DDIs), PBPK, PBPKPlus, PEAR, Population Estimates for Age-Related (PEAR™) Physiology™, tissue:plasma
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

The purpose of this modeling effort was to explore the effects of various processes and physiological parameters on the DDI involving competitive and time-dependent inhibition (TDI). Absorption and…

Single-Dose And Steady-State Pharmacokinetics Of Moxduo™, A Dual-Opioid Formulation Containing A Fixed Ratio Of Morphine And Oxycodone

Single-Dose And Steady-State Pharmacokinetics Of Moxduo™, A Dual-Opioid Formulation Containing A Fixed Ratio Of Morphine And Oxycodone

Authors: Webster L, Owen JS, Darling IM, Richards P, Kelen R, Stern W
Conference: American Pain Society (APS)
Keywords: accumulation index, central nervous, dose-normalized, female, general linear model, healthy, metabolites, neurology, noncompartmental, system agents, WinNonlin
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Q8003 (MoxDuo™) is the first dual-opioid combination product that has been evaluated in clinical trials. MoxDuo immediate-release capsules were developed for the management of acute moderate to severe…

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: Stone J, Jaworowicz DJ, Zajic S, Leung A, Duong LT, Passarell JA, Fiedler-Kelly J, Cohn D, Verbruggen N, Stoch A
Conference: International Symposium on Measurement and Kinetics of in vivo Drug Effects
Keywords: 1-compartment, biomarker, BSAP, dose-ranging, dose-response, exposure, geriatrics, Hill function, indirect response, Japanese, linear, LS-BMD, MK-0822, orthopedics, osteoclast, osteoporosis, resorption, saturable, turnover, uNTx, visual predictive check
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…

Prediction of Omeprazole’s Disposition and Drug-Drug Interactions Using A Physiologically-Based Pharmacokinetic Model

Prediction of Omeprazole’s Disposition and Drug-Drug Interactions Using A Physiologically-Based Pharmacokinetic Model

Authors: Lukacova V, Parrott N, Howard M, Woltosz WS, Bolger MB
Conference: ADMET Europe
Keywords: absorption, ACAT, advanced compartmental and transit (ACAT), DDIs, drug-drug interactions (DDIs), omeprazole, pharmacokinetics
Software: GastroPlus®
Division: PBPK

Download the poster presented at the ADMET Europe 2010 conference on the development of PBPK models and prediction of parent & metabolite DDIs with omeprazole.