The Combination of GIS and Biphasic to Better Predict In Vivo Dissolution of BCS Class IIb Drugs, Ketoconazole and Raloxifene

The Combination of GIS and Biphasic to Better Predict In Vivo Dissolution of BCS Class IIb Drugs, Ketoconazole and Raloxifene

Authors: Tsume Y, Igawa N, Drelich AJ, Amidon GE, Amidon GL
Publication: J Pharm Sci
Keywords: absorption modeling, ASD, BCS class II drug, biorelevant dissolution, gastrointestinal simulator, GIS, in vivo performance, ketoconazole, PBPK, raloxifene, simulation
Software: GastroPlus®

The formulation developments and the in vivo assessment of Biopharmaceutical Classification System (BCS) class II drugs are challenging due to their low solubility and high permeability in the...

Synaptophysin expression on circulating tumor cells in patients with castration resistant prostate cancer undergoing treatment with abiraterone acetate or enzalutamide

Synaptophysin expression on circulating tumor cells in patients with castration resistant prostate cancer undergoing treatment with abiraterone acetate or enzalutamide

Authors: Pal SK, He M, Chen L, Yang L, Pillai R, Twardowski P, Hsu J, Kortylewski M, Jones JO
Publication: Urol Oncol
Keywords: abiraterone, androgen receptor, Circulating tumor cell, enzalutamide, prostate cancer, Synaptophysin

Background: With the advent of secondary androgen receptor (AR)-targeted therapies in metastatic castration resistant prostate cancer (PC), nonadenocarcinoma PCs are...

Identification of mechanisms of resistance to treatment with abiraterone acetate or enzalutamide in patients with castration-resistant prostate cancer (CRPC)

Identification of mechanisms of resistance to treatment with abiraterone acetate or enzalutamide in patients with castration-resistant prostate cancer (CRPC)

Authors: Pal SK, Patel J, He M, Foulk B, Kraft K, Smirnov DA, Twardowski P, Kortylewski M, Bhargava V, Jones JO
Publication: Cancer
Keywords: androgen receptor, circulating tumor cells, RNA sequencing, targeted therapies

Background: Two androgen receptor (AR)-targeted therapies, enzalutamide and abiraterone acetate plus prednisone (abiraterone), have been approved for the treatment...

IVIVC using in silico and PBPK methods for inhaled drug product development

IVIVC using in silico and PBPK methods for inhaled drug product development

Authors: Lukacova V, Woltosz WS, Patterson B
Conference: DDL
Keywords: drug development, in silico, in vitro-in vivo correlation (IVIVC), inhaled, lung deposition, PBPK, pulmonary playlist
Software: GastroPlus®
Division: PBPK

The physiologically based model of the lung included in GastroPlus™ was used to simulate the absorption, distribution, and pharmacokinetics of two APIs from an inhaled combination product.

2017 White Paper: rise of hybrid LBA/LCMS immunogenicity assays (Part 2: hybrid LBA/LCMS biotherapeutics, biomarkers & immunogenicity assays and regulatory agencies’ inputs)

2017 White Paper: rise of hybrid LBA/LCMS immunogenicity assays (Part 2: hybrid LBA/LCMS biotherapeutics, biomarkers & immunogenicity assays and regulatory agencies’ inputs)

Authors: Neubert H, Song A, Lee A, Wei C, Duggan J, Xu K, Woolf E, Evans C, Palandra J, Laterza O, Amur S, Berger I, Bustard M, Cancilla M, Chen SC, Cho SJ, Ciccimaro E, Cludts I, Cocea L, D’Arienzo C, Danan-Leon L, Donato LD, Garofolo F, Haidar S, Ishii-Watabe A, Jiang H, Kadavil J, Kassim S, Kurki P, Blaye OL, Liu K, Mathews R, Santos GML, Niwa M, Pedras-Vasconcelos J, Qian M, Rago B, Saad O, Saito Y, Savoie N, Su D, Szapacs M, Tampal N, Vinter S, Wang J, Welink J, Whale E, Wilson A, Xue YJ
Publication: Bioanalysis
Keywords: bioanalysis, biotherapeutics, immunogenicity assays, LCMS, Workshop on Recent Issues in Bioanalysis (WRIB)
Division: Cheminformatics

The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place in Los Angeles/Universal City, California on 3-7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide.

Refining Liver Safety Risk Assessment: Application of Mechanistic Modeling and Serum Biomarkers to Cimaglermin Alfa (GGF2) Clinical Trials

Refining Liver Safety Risk Assessment: Application of Mechanistic Modeling and Serum Biomarkers to Cimaglermin Alfa (GGF2) Clinical Trials

Authors: Longo DM, Generaux GT, Howell BA, Siler SQ, Antoine DJ, Button D, Caggiano A, Eisen A, Iaci J, Stanulis R, Parry T, Mosedale M, Watkins PB
Publication: Clin Pharmacol Ther
Keywords: clinical trials, heart failure, hepatocytes, humans, protein growth, safety risk assessment, United States Food and Drug Administration
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Cimaglermin alfa (GGF2) is a recombinant human protein growth factor in development for heart failure.

Software based approaches for drug designing and development: A systematic review on commonly used software and its applications.

Software based approaches for drug designing and development: A systematic review on commonly used software and its applications.

Authors: Jamkhande P, Ghante MH, Ajgunde BR
Publication: Bulletin of the Faculty of Pharmacy, Cairo University
Keywords: absorption, Computational methods, dissolution, docking, drug discovery, formulation, molecular modeling, Structural activity relationship
Software: DDDPlus™, GastroPlus®

Drug discovery include drug designing and development, is a multifarious and expensive endeavor, where least number of drugs that pass the clinical trials makes it to market.

Phase 1 and pharmacokinetic study of LY3007113, a p38 MAPK inhibitor, in patients with advanced cancer

Phase 1 and pharmacokinetic study of LY3007113, a p38 MAPK inhibitor, in patients with advanced cancer

Authors: Goldman JW, Rosen LS, Tolcher AW, Papadopoulos K, Beeram M, Shi P, Pitou C, Bell RL, Kulanthaivel P, Zhang X, Fink A, Chan EM, Farrington D, Patnaik A
Publication: Investigational New Drugs
Keywords: creatine phosphokinase, LY3007113, MAPK-activated protein kinase 2, p38 MAPK inhibitor LY3007113, stomatitis
Division: PBPK

Background The signaling protein p38 mitogen-activated protein kinase (MAPK) regulates the tumor cell microenvironment, modulating cell survival, migration, and invasion.

Modeling of prolactin response following dopamine D2 receptor antagonists in rats: can it be translated to clinical dosing?

Modeling of prolactin response following dopamine D2 receptor antagonists in rats: can it be translated to clinical dosing?

Authors: Taneja A, Vermeulen A, Huntjens DRH, Danhof M, De Lange ECM, Proost JH
Publication: Pharmacol Res Perspect
Keywords: Agonist-antagonist interaction model, dopamine D2 antagonist, precursor pool model, prolactin, receptor occupancy, translational modeling
Division: PBPK

Prolactin release is a side effect of antipsychotic therapy with dopamine antagonists, observed in rats as well as humans.

2017 White Paper on recent issues in bioanalysis: aren’t BMV guidance/guidelines ‘Scientific’? (Part 1 – LCMS: small molecules, peptides and small molecule biomarkers)

2017 White Paper on recent issues in bioanalysis: aren’t BMV guidance/guidelines ‘Scientific’? (Part 1 – LCMS: small molecules, peptides and small molecule biomarkers)

Authors: Welink J, Yang E, Hughes N, Rago B, Woolf E, Sydor J, Coppola L, Ackermann B, Li W, Alley SC, Arnold M, Berger I, Briscoe C, Buonarati M, Bustard M, Cancilla M, Cho SJ, Duggan J, Fraier D, Garofolo F, Green R, Haidar S, Hittle L, Ishii-Watabe A, Islam R, Jenkins R, Jones B, Kadavil J, Kassim S, Kavetska O, Blaye OL, Lee A, Liu H, Mehl J, Santos GML, Musuku A, Ramanathan R, Saito Y, Savoie N, Summerfield S, Surapaneni S, Szapacs M, Tampal N, Verhaeghe T, Vinter S, Whale E
Publication: Bioanalysis
Keywords: bioanalysis, biomarkers, immunogenicity, LCMC, mall Molecules, Scientific, Workshop on Recent Issues in Bioanalysis (WRIB)
Division: Cheminformatics

The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place in Los Angeles/Universal City, California from 3 April 2017 to 7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide.

A cross-species translational pharmacokinetic-pharmacodynamic evaluation of core bodytemperature reduction by the TRPM8 blocker PF-05105679.

A cross-species translational pharmacokinetic-pharmacodynamic evaluation of core bodytemperature reduction by the TRPM8 blocker PF-05105679.

Authors: Gosset JR, Beaumont K, Matsuura T, Winchester W, Attkins N, Glatt S, Lightbown I, Ulrich K, Roberts S, Harris J, Mesic E, van Steeg T, Hijdra D, van der Graaf PH
Publication: Eur J Pharm Sci
Keywords: allometry, mechanistic absorption, PBPK modeling, qsp
Software: GastroPlus®
Division: PBPK

PF-05105679 is a moderately potent TRPM8 blocker which has been evaluated for the treatment of cold pain sensitivity.

Modeling of Active Transport and Metabolism for Hepatocyte Assays with Application of In Vitro to In Vivo Extrapolation (IVIVE)

Modeling of Active Transport and Metabolism for Hepatocyte Assays with Application of In Vitro to In Vivo Extrapolation (IVIVE)

Authors: Mullin JM, Lukacova V, Woltosz WS, Bolger MB
Conference: AAPS
Keywords: active transport, drug-drug interactions (DDIs), hepatocyte assays, In vitro in vivo extrapolation (IVIVE), metabolism
Software: MembranePlus™

Sandwich and suspended hepatocyte cultures are routinely used to assess either active transport and/or metabolism of drug molecules. 

Development of In Vitro-In Vivo Correlation for Long Acting Injectable Microsphere Formulations

Development of In Vitro-In Vivo Correlation for Long Acting Injectable Microsphere Formulations

Authors: Shahraz A, Mullin JM, Spires J, Lukacova V, Bolger MB, Woltosz WS
Conference: AAPS
Keywords: In vitro in vivo correlations (IVIVC), injectable microsphere formulations, pharmacokinetics of LAI microspheres, polymer degradation
Software: GastroPlus®
Division: PBPK

The concept of in vitro-in vivo correlations (IVIVCs) for long-acting injectable (LAI) microsphere formulations has gained more significance in the past decade.

Application of Physiologically Based Pharmacokinetic (PBPK) Models in Predicting Drug Pharmacokinetics for Different Ethnic Groups

Application of Physiologically Based Pharmacokinetic (PBPK) Models in Predicting Drug Pharmacokinetics for Different Ethnic Groups

Authors: Szeto KX, Lukacova V, Li M, Zhou H, DiBella J, Woltosz WS, Bolger MB
Conference: AAPS
Keywords: Caucasian, Chinese, drug pharmacokinetics, Physiologically based pharmacokinetic (PBPK) modeling
Software: GastroPlus®
Division: PBPK

The purpose of this study was to evaluate the ability of PBPK models to predict the pharmacokinects (PK) of different compounds in two ethnic groups, Caucasian and Chinese.