An in vitro toolbox to accelerate anti-malarial drug discovery and development

An in vitro toolbox to accelerate anti-malarial drug discovery and development

Authors: Charman SA, Andreu A, Barker H, Blundell S, Campbell A, Campbell M, Chen G, Chiu FCK, Crighton E, Katneni K, Morizzi J, Patil R, Pham T, Ryan E, Saunders J, Shackleford DM, White KL, Almond L, Dickins M, Smith DA, Burrows JN, Abla N
Publication: Malaria Journal
Keywords: admet predictor, drug discovery, gastroplus, machine learning, pbbm, PBPK modeling
Software: ADMET Predictor®, GastroPlus®

Modelling and simulation are being increasingly utilized to support the discovery and development of new anti-malarial drugs.

Integrated phytochemical analysis based on UHPLC-LTQ–Orbitrap and network pharmacology approaches to explore the potential mechanism of Lycium ruthenicum Murr. for ameliorating Alzheimer’s disease

Integrated phytochemical analysis based on UHPLC-LTQ–Orbitrap and network pharmacology approaches to explore the potential mechanism of Lycium ruthenicum Murr. for ameliorating Alzheimer’s disease

Authors: Luo Z, Yu G, Chen X, Liu Y, Zhou Y, Wang G, Shi Y
Publication: Food & Function
Keywords: alzheimer's disease, folk medicines, mechanistic, pharmacology
Software: ADMET Predictor®

Based on compelling experimental and clinical evidence, the fruit of Lycium ruthenicum Murr. (LRM), a unique traditional Tibetan medicine...

Allosteric regulation of protein 14-3-3ζ scaffold by small-molecule editing modulates histone H3 post-translational modifications

Allosteric regulation of protein 14-3-3ζ scaffold by small-molecule editing modulates histone H3 post-translational modifications

Authors: Wan YJ, Liao LX, Liu Y, Yang H, Song XM, Wang LC, Zhang XW, Qian Y, Liu D, Han LW, Xia Q, Liu KC, Du ZY, Jiang Y, Zhao MB, Zeng KW, Tul PF
Publication: Theranostics
Keywords: 14-3-3ζ, allosteric effect, autophagy-lysosome function, endoplasmic reticulum stress, Histone post-translational modifications
Software: ADMET Predictor®

Histone post-translational modifications (PTMs) are involved in various biological processes such as transcriptional...

Relationship between plasma concentrations and clinical effects of cariprazine in patients with schizophrenia or bipolar mania

Relationship between plasma concentrations and clinical effects of cariprazine in patients with schizophrenia or bipolar mania

Authors: Periclou A, Willavize S, Jaworowicz DJ, Passarell JA, Carrothers T, Ghahramani P, Durgam S, Earley W, Kapás M, Khariton T
Publication: Clin Transl Sci
Keywords: bipolar mania, cariprazine, cognigen consulting, plasma concentrations, schizophrenia
Division: Cognigen

Population pharmacokinetic/pharmacodynamic modeling (via NONMEM) was used to describe longitudinal exposure-response...

Developing Clinically Relevant Dissolution Specifications for Oral Drug Products-Industrial and Regulatory Perspectives

Developing Clinically Relevant Dissolution Specifications for Oral Drug Products-Industrial and Regulatory Perspectives

Authors: McAllister M, Flanagan T, Boon K, Pepin X, Tistaert C, Jamei M, Abend A, Kotzagiorgis E, Mackie CE
Publication: Pharmaceutics
Keywords: bioequivalence, biowaivers, dissolution specifications, gastroplus, pbbm, PBPK modeling, physiologically based biopharmaceutics model, product specifications
Software: GastroPlus®

A meeting that was organized by the Academy of Pharmaceutical Sciences Biopharmaceutics and Regulatory Sciences focus groups focused on the challenges of...

Biowaiver Applications in Support of a Polymorph During Late-Stage Clinical Development of Verubecestat—Current Challenges and Future Opportunities for Global Regulatory Alignment

Biowaiver Applications in Support of a Polymorph During Late-Stage Clinical Development of Verubecestat—Current Challenges and Future Opportunities for Global Regulatory Alignment

Authors: Abend A, Xiong L, Zhang X, Frankenfeld C, Kesisoglou F, Reuter K, Kotwal P
Publication: AAPS J
Keywords: BCS, bioequivalence, biopharmaceutics, biowaivers, dissolution, gastroplus, ICH M9, mechanistic absorption model, pbbm, PBPK modeling, product specifications
Software: GastroPlus®

Dissolution experiments to support an active pharmaceutical ingredient (API) form change in Verubecestat immediate release tablets were performed following...

2′-Hydroxychalcones as an alternative treatment for trichomoniasis in association with metronidazole

2′-Hydroxychalcones as an alternative treatment for trichomoniasis in association with metronidazole

Authors: Neves RN, Sena-Lopes A, Alves MSD, da Rocha Fonseca B, da Silva CC, Casaril AM, Savegnago L, de Pereira CMP, Ramos DF, Borsuk F
Publication: Parasit Res
Keywords: Chalcones, molecular docking, Synthesis, T. vaginalis
Software: ADMET Predictor®

The treatment for trichomoniasis, based on 5′-nitroimidazol agents, has been presenting failures related to allergic reactions, side effects, and the emergence of resistant isolates.

Prediction characteristics of oral absorption simulation software evaluated using structurally diverse low solubility drugs

Prediction characteristics of oral absorption simulation software evaluated using structurally diverse low solubility drugs

Authors: Matsumura N, Hayashi S, Akiyama Y, Ono A, Funaki S, Tamura N, Kimoto T, Jiko M, Haruna Y, Sarashina A, Ishida M, Nishiyama K, Fushimi M, Kojima Y, Yoneda K, Nakanishi M, Kim S, Fujita T, Sugano K
Publication: J Pharm Sci
Keywords: biopharmaceutics, dissolution, gastroplus, mechanistic absorption modeling, oral absorption, pbbm, PBPK modeling, permeability, physiologically based pharmacokinetic modeling, simulation
Software: GastroPlus®

The purpose of the present study was to characterize current biopharmaceutics modeling and simulation software regarding the prediction of the fraction of a dose absorbed (Fa) in humans.

Prediction Characteristics of Oral Absorption Simulation Software Evaluated Using Structurally Diverse Low-Solubility Drugs

Prediction Characteristics of Oral Absorption Simulation Software Evaluated Using Structurally Diverse Low-Solubility Drugs

Authors: Matsumura N, Hayashi S, Akiyama Y, Ono A, Funaki S, Tamura N, Kimoto T, Jiko M, Haruna Y, Sarashina A, Ishida M, Nishiyama K, Fushimi M, Kojima Y, Yoneda K, Nakanishi M, Kim S, Fujita T, Sugano K
Publication: J Pharm Sci
Keywords: dissolution, oral absorption, permeability, simulation, solubility
Software: ADMET Predictor®

The purpose of the present study was to characterize current biopharmaceutics modeling and simulation software regarding the prediction of the fraction of a dose absorbed (Fa) in humans.

Application of physiologically based kinetic (PBK) modelling in the next generation risk assessment of dermally applied consumer products

Application of physiologically based kinetic (PBK) modelling in the next generation risk assessment of dermally applied consumer products

Authors: Moxon TE, Li H, Lee MY, Piechota P, Nicol B, Pickles J, Pendlington R, Sorrell I, Baltazar MT
Publication: Toxicol In Vitro
Keywords: consumer goods, dermal absorption, gastroplus, pbbm, PBPK modeling, physiologically based pharmacokinetics
Software: ADMET Predictor®, GastroPlus®

Next Generation Risk Assessment (NGRA) is a procedure that integrates new approach methodologies (NAMs) to assure safety of a product without generating data from animal testing.

Pharmacokinetics of the Monocarboxylate Transporter 1 Inhibitor AZD3965 in Mice: Potential Enterohepatic Circulation and Target-Mediated Disposition

Pharmacokinetics of the Monocarboxylate Transporter 1 Inhibitor AZD3965 in Mice: Potential Enterohepatic Circulation and Target-Mediated Disposition

Authors: Guan X, Morris ME
Publication: Pharm Res
Keywords: admet predictor, AZD3965, enterohepatic cycling, monocarboxylate transporters, pharmacokinetics, target-mediated drug disposition
Software: ADMET Predictor®, MedChem Designer™

To evaluate the pharmacokinetics (PK) of the monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 in mice after IV and oral administration and to develop mechanistic PK models to assess the potential...

Development of Novel Oxotriazinoindole Inhibitors of Aldose Reductase: Isosteric Sulfur/Oxygen Replacement in the Thioxotriazinoindole Cemtirestat Markedly Improved Inhibition Selectivity

Development of Novel Oxotriazinoindole Inhibitors of Aldose Reductase: Isosteric Sulfur/Oxygen Replacement in the Thioxotriazinoindole Cemtirestat Markedly Improved Inhibition Selectivity

Authors: Hlavac M, Kovacikova L, Prnova MS, Sramel P, Addova G, Majekova M, Hanquet G, Bohac A, Stefek M
Publication: J Med Chem
Keywords: inhibition, inhibitors, molecular structure, peptides, proteins, selectivity
Software: ADMET Predictor®

Inhibition of aldose reductase (AR), the first enzyme of the polyol pathway, is a promising approach in treatment of diabetic complications.

2019 White Paper On Recent Issues in Bioanalysis: FDA BMV Guidance, ICH M10 BMV Guideline and Regulatory Inputs ( Part 2 – Recommendations on 2018 FDA BMV Guidance, 2019 ICH M10 BMV Draft Guideline and Regulatory Agencies’ Input on Bioanalysis, Biomarkers and Immunogenicity)

2019 White Paper On Recent Issues in Bioanalysis: FDA BMV Guidance, ICH M10 BMV Guideline and Regulatory Inputs ( Part 2 – Recommendations on 2018 FDA BMV Guidance, 2019 ICH M10 BMV Draft Guideline and Regulatory Agencies’ Input on Bioanalysis, Biomarkers and Immunogenicity)

Authors: Booth B, Stevenson L, Pillutla R, Buonarati M, Beaver C, Fraier D, Garofolo F, Haidar S, Islam R, James C, Kadavil J, Kavetska O, Li F, Satterwhite C, Savoie N, Subramaniam S, Tampal N, Thway T, Woolf E, Blaye OL, Andisik M, Briscoe C, Dasgupta A, Fischer S, Hayes R, Kamerud J, Santos GML, Nehls C, Soo C, Vinter S, Whale E, Xu K, Cho SJ, Edmison A, Kassim S, Rocha TC, Welink J, Amur S, Bandukwala A, Cherry E, Hopper S, Ishii-Watabe A, Kirshner S, Maher K, Pedras-Vasconcelos J, Saito Y, Saunders TS, Skibeli V, Verthelyi D, Wang YM, Yan H
Publication: Bioanalysis
Division: Simulations Plus

The 2019 13th Workshop on Recent Issues in Bioanalysis (WRIB) took place in New Orleans, LA on 1-5 April 2019 with an attendance of over 1000 representatives from...

In vitro–In vivo Relationship and Bioequivalence Prediction for Modified-Release Capsules Based on a PBPK Absorption Model

In vitro–In vivo Relationship and Bioequivalence Prediction for Modified-Release Capsules Based on a PBPK Absorption Model

Authors: Jereb R, Opara J, Legen I, Petek B, Grabnar-Peklar D
Publication: AAPS PharmSciTech
Keywords: controlled release, gastroplus, IVIVC, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics modeling, virtual bioequivalence
Software: GastroPlus®

A physiologically based pharmacokinetic (PBPK) absorption model was developed in GastroPlus™ based on data on intravenous, immediate-release (IR), and modified-release (MR) drug products.thought