Ribociclib Bioavailability Is Not Affected by Gastric pH Changes or Food Intake: In Silico and Clinical Evaluations.

Ribociclib Bioavailability Is Not Affected by Gastric pH Changes or Food Intake: In Silico and Clinical Evaluations.

Authors: Samant TS, Dhuria S, Lu Y, Laisney M, Yang S, Grandeury A, Mueller-Zsigmondy M, Umehara K, Huth F, Miller M, Germa C, Elmeliegy M
Publication: Clin Pharmacol Ther
Keywords: absorption, ddI, drug labeling, drug–drug interaction, gastric pH, PBPK modeling, PPI, stomach
Software: GastroPlus®

Ribociclib (KISQALI®), a cyclin-dependent kinase 4/6 inhibitor approved for the first-line treatment of HR+/HER2– advanced breast cancer with an aromatase inhibitor, is administered with...

Intrinsic dissolution simulation of highly and poorly soluble drugs for BCS solubility classification

Intrinsic dissolution simulation of highly and poorly soluble drugs for BCS solubility classification

Authors: Duque MD, Issa MG, Silva DA, Kakuda BAS, Rodrigues LNC, Löbenberg R, Ferraz HG
Publication: Dissolut Technol
Keywords: api, BCS, dissolution, in vitro dissolution, intrinsic, intrinsic dissolution rate, metronidazole, pyrimethamine
Software: DDDPlus™

Intrinsic dissolution testing allows characterizing drug substances through its dissolution rate when exposed to a specified surface area in a specific dissolution media.

Combining “Bottom-up” and “Top-down” Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC-0941) Pharmacokinetics

Combining “Bottom-up” and “Top-down” Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC-0941) Pharmacokinetics

Authors: Lu T, Fraczkiewicz G, Salphati L, Budha N, Dalziel G, Smelick GS, Morrissey KM, Davis JD, Jin JY, Ware JA
Publication: CPT Pharmacometrics Syst Pharmacol
Keywords: food effect, gastric emptying, gastric pH, mechanistic absorption, PBPK, PPI, proton pump, stomach pH
Software: GastroPlus®
Division: PBPK

Pictilisib, a weakly basic compound, is an orally administered, potent, and selective pan-inhibitor of phosphatidylinositol 3-kinases for oncology indications.

Predictive Biopharmaceutics and Pharmacokinetics: Modeling and Simulation

Predictive Biopharmaceutics and Pharmacokinetics: Modeling and Simulation

Authors: Yang Y, Zhao Y, Duan JZ, Zhao P, Zhao L, Zhang X
Publication: Developing solid oral dosage forms : pharmaceutical theory & practice
Keywords: absorption, biopharmaceutics, dissolution, formulations, modeling and simulation, PBPK, pharmacodynamics (PD), pharmacokinetics (PK)
Software: GastroPlus®

Scientists have made great discoveries concerning human physiology and gained tremendous knowledge during drug development efforts.

Investigating the state of physiologically based kinetic modelling practices and challenges associated with gaining regulatory acceptance of model applications.

Investigating the state of physiologically based kinetic modelling practices and challenges associated with gaining regulatory acceptance of model applications.

Authors: Paini A, Leonard JA, Kliment T, Tan YM, Worth A
Publication: Regul Toxicol Pharmacol
Keywords: FIHSimulator, first-in-human, Physiologically-based toxicokinetic (PBTK) modelling, safety research, toxicology
Software: GastroPlus®

Physiologically based kinetic (PBK) models are used widely throughout a number of working sectors, including academia and industry, to provide insight into the dosimetry related to observed adverse...

Effect of the pulmonary deposition and in vitro permeability on the prediction of plasma levels of inhaled budesonide formulation

Effect of the pulmonary deposition and in vitro permeability on the prediction of plasma levels of inhaled budesonide formulation

Authors: Salar-Behzadi S, Wu S, Mercuri A, Meindl C, Stranzinger S, Fröhlich E
Publication: Int J Pharm
Keywords: additional dosage routes, budesonide, in silico, lung deposition, nasal, plasma profile, pulmonary absorption, pulmonary permeability, pulmonary playlist, simulation
Software: GastroPlus®

The growing interest in the inhalable pharmaceutical products requires advanced approaches to safe and fast product development, such as in silico tools that can be used...

Abstract B083: Population pharmacokinetics and pharmacodynamics for an oral Notch inhibitor, LY3039478, in patients with advanced cancer and healthy volunteers

Abstract B083: Population pharmacokinetics and pharmacodynamics for an oral Notch inhibitor, LY3039478, in patients with advanced cancer and healthy volunteers

Authors: Yuen E, Bell RL, Posada M, Massard C, Rodon J, Smith C, Thorn K, Diener JT, Ortega D, Suico J, Benhadji K
Keywords: First Human Dose, LY3039478, NONMEM, Notch Intracellular Domain (NICD), PK/PD
Division: PBPK

Background: LY3039478 is an oral Notch inhibitor that prevents release of the Notch Intracellular Domain (NICD) by inhibiting proteolytic activity of the gamma (γ)-secretase complex.

Identification of impurities in macrolides by liquid chromatography–mass spectrometric detection and prediction of retention times of impurities by constructing quantitative structure–retention relationship (QSRR)

Identification of impurities in macrolides by liquid chromatography–mass spectrometric detection and prediction of retention times of impurities by constructing quantitative structure–retention relationship (QSRR)

Authors: Zhang X, Li J, Wang C, Song D, Hu CQ
Publication: J Pharm Biomed Anal
Keywords: impurity profiling, liquid chromatography tandem mass spectrometry, quantitative structure-retention relationships
Software: ADMET Predictor®

Macrolides are multicomponent drugs whose impurity control is always a challenge demanding analysis method with good sensitivity and selectivity.

Industry’s View on Using Quality Control, Biorelevant, and Clinically Relevant Dissolution Tests for Pharmaceutical Development, Registration, and Commercialization.

Industry’s View on Using Quality Control, Biorelevant, and Clinically Relevant Dissolution Tests for Pharmaceutical Development, Registration, and Commercialization.

Authors: Grady H, Elder DP, Webster GK, Mao Y, Lin Y, Flanagan T, Mann J, Blanchard A, Cohen MJ, Lin J, Kesisoglou F, Hermans A, Abend A, Zhang L, Curran D
Publication: J Pharm Sci
Keywords: absorption, biorelevant, clinically relevant, dissolution, drug release, PBPK, pharmacokinetics, quality control
Software: GastroPlus®

This article intends to summarize the current views of the IQ Consortium Dissolution Working Group, which comprises various industry companies, on the roles of dissolution testing throughout...

Population Pharmacokinetics (PK) and Exposure-Efficacy Analyses of Nivolumab in Subjects with Advanced Hepatocellular Carcinoma (HCC)

Population Pharmacokinetics (PK) and Exposure-Efficacy Analyses of Nivolumab in Subjects with Advanced Hepatocellular Carcinoma (HCC)

Authors: Wang X, Ludwig EA, Passarell C, Boone B, Baakili A, Dela Cruz C, Roy A, Hruska M
Conference: ACoP
Keywords: exposure-efficacy analyses, hepatocellular carcinoma (HCC), nivolumab, Oncology, population pharmacokinetics
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Nivolumab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody (mAb) that selectively binds to the programmed death-1 (PD-1) membrane receptor. PD-1 is a negative regulatory molecule expressed...