Best Practices for Integration of Dissolution Data into Physiologically Based Biopharmaceutics Models (PBBM): A Biopharmaceutics Modeling Scientist Perspective

Best Practices for Integration of Dissolution Data into Physiologically Based Biopharmaceutics Models (PBBM): A Biopharmaceutics Modeling Scientist Perspective

Authors: Kollipara S, Bhattiprolu AK, Boddu R, Ahmed T, Chachad S
Publication: AAPS PharmSciTech
Keywords: biopharmaceutics, dddplus, drug product specifications, gastroplus, in vitro method, pbbm, PBPK modeling, physiologically based pharmacokinetics, virtual bioequivalence
Software: GastroPlus®

Dissolution is considered as a critical input into physiologically based biopharmaceutics models (PBBM) as it governs in vivo exposure. Despite many workshops, initiatives...

Identification of the Putative Binding Site of a Benzimidazole Opioid (Etazene) and Its Metabolites at µ-Opioid Receptor: A Human Liver Microsomal Assay and Systematic Computational Study

Identification of the Putative Binding Site of a Benzimidazole Opioid (Etazene) and Its Metabolites at µ-Opioid Receptor: A Human Liver Microsomal Assay and Systematic Computational Study

Authors: Chaturvedi P, Hewamanna I, Pandey P, Khan W, Wang YH, Chittiboyina AG, Doerksen RJ, Godfrey M
Publication: Molecules
Keywords: docking, etazene, liver microsomal assay, molecular dynamics mu-opioid receptor, synthetic opioids
Software: ADMET Predictor®
Therapeutic Areas: CNS

The synthetic benzimidazole opioid etazene (which has a 70-times higher analgesic activitythan morphine), a recreational drug, has gained popularity as a...

Addressing the oxamniquine in vitro-in vivo paradox to facilitate a new generation of anti-schistosome treatments

Addressing the oxamniquine in vitro-in vivo paradox to facilitate a new generation of anti-schistosome treatments

Authors: Toth K, Alwan S, Khan S, McHardy SF, LoVerde PT, Cameron MD
Publication: Intl J Parasit Drugs and Drug Resistance
Keywords: Oxamniquine, Parasitic worm, PK/PD relationship, Schistosome, Schistosomiasis
Software: ADMET Predictor®
Therapeutic Areas: Anti-effective

The antischistosomal drug oxamniquine, OXA, requires activation by a sulfotransferase within the parasitic worm to enable killing.

An Insight into the Metabolism of 2,5-Disubstituted Monotetrazole Bearing Bisphenol Structures: Emerging Bisphenol A Structural Congeners

An Insight into the Metabolism of 2,5-Disubstituted Monotetrazole Bearing Bisphenol Structures: Emerging Bisphenol A Structural Congeners

Authors: Gadgoli UB, Sunil Kumar YC, Kumar D
Publication: Molecules
Keywords: biotransformation pathway, bisphenol acetone, CYP inhibition assay, in silico assessment, Molecular dynamic simulations, single-concentration Kobs assay, substrate depletion assay, tetrazole bisphenol
Software: ADMET Predictor®

The non-estrogenic 2,5-disubstituted tetrazole core-bearing bisphenol structures (TbB) are being researched as emerging structural congeners of Bisphenol...

An innovative impurity profiling of esmolol hydrochloride injection using UPLC-MS based multiple mass defect filter, chemometrics and in-silico toxicity prediction

An innovative impurity profiling of esmolol hydrochloride injection using UPLC-MS based multiple mass defect filter, chemometrics and in-silico toxicity prediction

Authors: Zhang B, Li WB, Wang Q, Liu XY, Liu YM, Huang HP, Hu B, Yin S, Wang YK
Publication: Arab J Chem
Keywords: EsmololUPLC-MS/MS based chemometrics, Impurity profile, Multiple mass defect filter, Toxicity predication
Software: ADMET Predictor®

Esmolol hydrochloride injection is indicated for the rapid control of ventricular rate in patients with atrial fibrillation or atrial flutter in perioperative...

Prediction model for milk transfer of drugs by primarily evaluating the area under the curve using QSAR/QSPR

Prediction model for milk transfer of drugs by primarily evaluating the area under the curve using QSAR/QSPR

Authors: Maeshima T, Yoshida S, Watanabe M, Itagaki F
Publication: Pharm Res
Keywords: admet predictor, artificial intelligence, machine learning, neural networks, pregnancy, structure-activity relationship
Software: ADMET Predictor®

Information on milk transferability of drugs is important for patients who wish to breastfeed. The purpose of this study is to develop a prediction model for milk-to-plasma...

Alternative Pharmacokinetic Metrics in Single-Dose Studies to Ensure Bioequivalence of Prolonged-Release Products at Steady State-A Case Study

Alternative Pharmacokinetic Metrics in Single-Dose Studies to Ensure Bioequivalence of Prolonged-Release Products at Steady State-A Case Study

Authors: Mangas-Sanjuán V, Simón M, González-Rojano E, Ochoa D, Abad-Santos F, Román M, Ramos M, Govantes C, Garcia-Arieta A
Publication: Pharmaceutics
Keywords: bioequivalence, pAUC, prolonged release, single-dose, steady state

This article investigates which PK metrics in a single-dose study (con-centration at the end of posology interval, Cτ, partial areas under the curve, pAUCs, or half-valueduration, HVD) are more sensitive and less variable...

Quickening the Pace of Drug Discovery with AI
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Quickening the Pace of Drug Discovery with AI

Authors: Levine D, Jamois E, Lawless M, Jones J
Keywords: admet predictor, AIDD, Artificial Intelligence-driven Drug Discovery (AIDD), gastroplus, machine learning, PBPK modeling
Software: ADMET Predictor®, GastroPlus®

“The integration of our industry-leading ADMET Predictor and GastroPlus® mechanistic PBPK simulations into the initial generative chemical design process is what sets us apart from other machine learning drug design companies,” says AIDD Principal Scientist and former City of Hope Professor Jeremy Jones. “Our platform offers everything a medicinal chemist would want, at incredible speed.”

Lowly-buffered biorelevant dissolution testing is not necessarily biopredictive of human bioequivalence study outcome: Relationship between dissolution and pharmacokinetics

Lowly-buffered biorelevant dissolution testing is not necessarily biopredictive of human bioequivalence study outcome: Relationship between dissolution and pharmacokinetics

Authors: Matsui K, Nakamichi K, Nakatani M, Yoshida H, Yamashita S, Yokota S
Publication: Int J Pharm
Keywords: ACAT, bioequivalence, biopharmaceutics, dissolution method, gastroplus, mechanistic absorption, pbbm, PBPK modeling, physiologically based pharmacokinetics, vbe
Software: GastroPlus®

It has been revealed that buffer capacity of aspirated human intraluminal fluid is much lower than that of in vitro compendial dissolution media. Since buffer capacity signif

Investigating bile acid-mediated cholestatic drug-induced liver injury using a mechanistic model of multidrug resistance protein 3 (MDR3) inhibition

Investigating bile acid-mediated cholestatic drug-induced liver injury using a mechanistic model of multidrug resistance protein 3 (MDR3) inhibition

Authors: Beaudoin J, Yang K, Adiwidjaja J, Taneja G, Watkins PB, Siler SQ, Howell BA, Woodhead JL
Publication: Frontiers in Pharmacology
Keywords: bile acids, cholangiocyte toxicity, cholehepatic, MDR3, MDR3 inhibition
Software: DILIsym®
Division: Simulations Plus

Inhibition of the canalicular phospholipid floppase multidrug resistance protein 3 (MDR3) has been implicated in cholestatic drug-induced liver injury (DILI), which is clinically...

N-Derivatives of (Z)-Methyl 3-(4-Oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylates as Antimicrobial Agents—In Silico and In Vitro Evaluation

N-Derivatives of (Z)-Methyl 3-(4-Oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylates as Antimicrobial Agents—In Silico and In Vitro Evaluation

Authors: Pertrou A, Geronikaki A, Kartsev V, Kousaxidis A, Papadimitriou-Tsantarliotou A, Kostic M, Ivanov M, Nicolaou I, IS Vizirianakis
Publication: Pharmaceuticals
Keywords: ADMET, antibacterial activity, antifungal activity, antimicrobial, cytotoxicity, Indole, molecular docking, rhodamine
Software: ADMET Predictor®
Therapeutic Areas: Anti-effective

Herein, we report the experimental evaluation of the antimicrobial activity of seventeen new (Z)-methyl 3-(4-oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylate derivatives.

Therapeutic target mapping from the genome of Kingella negevensis and biophysical inhibition assessment through PNP synthase binding with traditional medicinal compounds

Therapeutic target mapping from the genome of Kingella negevensis and biophysical inhibition assessment through PNP synthase binding with traditional medicinal compounds

Authors: Basharat Z, Murtaza Z, Siddiqa A, Alnasser SM, Meshal A
Publication: Mol Divers
Keywords: biopharmaceutics, disease states, gastroplus, hepatic impairment, pbbm, PBPK modeling, physiologically based pharmacokinetics, population simulations
Software: GastroPlus®

Kingella negevensis belongs to the Neisseriaceae family. It is implied that it has significant virulence potential due to RTX toxin production, which can cause hemolysis.

Cationic nanoliposomes of carvedilol for intranasal application: In vitro, in vivo and in silico studies

Cationic nanoliposomes of carvedilol for intranasal application: In vitro, in vivo and in silico studies

Authors: Kar S, Singh SK
Publication: J Drug Deliv Sci Technol
Keywords: gastroplus, inhaled drug product, nasal delivery, pbbm, PBPK modeling, pcat, physiologically based pharmacokinetics, pulmonary absorption
Software: GastroPlus®

Carvedilol (CVD) is a non-selective β and α adrenoreceptor blocker, useful in treating hypertension, angina pectoris, congestive heart failure (CHF), and coronary artery...

Safety, Tolerability, and Pharmacokinetics of Nebulized Hydroxychloroquine: A Pilot Study in Healthy Volunteers

Safety, Tolerability, and Pharmacokinetics of Nebulized Hydroxychloroquine: A Pilot Study in Healthy Volunteers

Authors: Hawari F, Dodin Y, Tayyem R, Najjar S, Kakish H, Fara MA, Zou’bi AA, Idkaidek N
Publication: J Aerosol Med Pulm Drug Deliv
Keywords: gastroplus, inhaled drug product, pbbm, PBPK modeling, pcat, physiologically based pharmacokinetics, pulmonary absorption
Software: GastroPlus®

Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, hydroxychloroquine (HCQ) drew substantial attention as a potential COVID-19 treatment...