Population pharmacokinetic (PopPK) and concentration-QTc analysis of quizartinib in patients (pts) with FLT3-ITD–positive relapsed/refractory (R/R) acute myeloid leukemia (AML)

Population pharmacokinetic (PopPK) and concentration-QTc analysis of quizartinib in patients (pts) with FLT3-ITD–positive relapsed/refractory (R/R) acute myeloid leukemia (AML)

Authors: Kang D, Ludwig EA, Jaworowicz DJ, Huang H, Fiedler-Kelly J, Cortes J, Ganguly S, Khaled S, Krämer A, Levis M, Martinelli G, Perl A, Russell N, Abutarif M, Choi Y, Kobayashi K, Mendell J, Yin O
Conference: European Hematology Association (EHA)
Keywords: Fms-related tyrosine kinase 3, Quizartinib
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Fms-related tyrosine kinase 3 (FLT3) is expressed in hematopoietic progenitor cells;
signaling through FLT3 promotes their proliferation and differentiation. FLT3 is mutated
in approximately 30% of patients with AML.

Harnessing Human Microphysiology Systems as Key Experimental Models for Quantitative Systems Pharmacology

Harnessing Human Microphysiology Systems as Key Experimental Models for Quantitative Systems Pharmacology

Authors: Taylor DL, Gough A, Schurdak ME, Vernetti L, Chennubhotla C, Lefever D, Pei F, Faeder JR, Lezon TR, Stern AM, Bahar I
Publication: Handb Exp Pharmacol
Keywords: Computational models of ADME-Tox, Computational models of disease, DILI, drug development, drug discovery, Drug repurposing, Induced pluripotent stem cells, Microphysiology systems, Omics analyses, PBPK, Personalized medicine, quantitative systems pharmacology, toxicology
Software: ADMET Predictor®

Two technologies that have emerged in the last decade offer a new paradigm for modern pharmacology, as well as drug discovery and development.

Uncovering the pharmacological mechanism of Carthamus tinctorius L. on cardiovascular disease by a systems pharmacology approach

Uncovering the pharmacological mechanism of Carthamus tinctorius L. on cardiovascular disease by a systems pharmacology approach

Authors: Yu G, Luo Z, Zhou Y, Zhang L, Wu Y, Ding L, Shi Y
Publication: Biomed Pharmacother
Keywords: Cardiovascular disease, Carthamus tinctorius L., Platelet activation, Systems pharmacology, Traditional Chinese Medicine
Software: ADMET Predictor®

Carthamus tinctorius L. is widely used in traditional Chinese medicines for the treatment of cardiovascular disease.

“Development of Fixed Dose Combination Products” Workshop Report: Considerations of Gastrointestinal Physiology and Overall Development Strategy

“Development of Fixed Dose Combination Products” Workshop Report: Considerations of Gastrointestinal Physiology and Overall Development Strategy

Authors: Hens B, Corsetti M, Bermejo M, Löbenberg R, González PM, Mitra A, Desai D, Chilukuri DM, Aceituno A
Publication: AAPS J
Keywords: dissolution, formulation design, mechanistic absorption model, pbbm, PBPK modeling, precipitation
Software: GastroPlus®

The gastrointestinal (GI) tract is one of the most popular and used routes of drug product administration due to the convenience for better patient compliance and reduced costs to the patient compared to other routes.

Investigation of potent inhibitors of cholinesterase based on thiourea and pyrazoline derivatives: Synthesis, inhibition assay and molecular modeling studies

Investigation of potent inhibitors of cholinesterase based on thiourea and pyrazoline derivatives: Synthesis, inhibition assay and molecular modeling studies

Authors: Mumtaz A, Majeed A, Zaib S, Rahman S, Hameed S, Saeed A, Rafique H, Mughal E, Maalik A, Hussain I, Iqbal J
Publication: Bioorg Chem
Keywords: alzheimer disease, Chalcones, Enzyme inhibition, ibuprofen, Pyrazolines, Triazole
Software: ADMET Predictor®

Owing to the desperate need of new drugs development to treat Alzheimer's ailment the synthesis of 1-aroyl-3-(5-(4-chlorophenyl)-1,2,4-triazole-3-thioneaminylthioureas (2–6)...

Ceftolozane/tazobactam population pharmacokinetics and dose selection for further clinical evaluation in pediatric patients with complicated urinary tract or complicated intraabdominal infections

Ceftolozane/tazobactam population pharmacokinetics and dose selection for further clinical evaluation in pediatric patients with complicated urinary tract or complicated intraabdominal infections

Authors: Larson KB, Patel Y, Willavize S, Bradley JS, Rhee EG, Caro L, Rizk ML
Publication: Antimicrob Agents Chemother
Keywords: cephalosporin, children, cognigen consulting, enterobacterales, pseudomonas, target attainment
Division: Quantitative Systems Pharmacology (QSP)

Ceftolozane-tazobactam, a combination of the novel antipseudomonal cephalosporin ceftolozane and the...

In Silico Design of Dapsone Analogues Effective Towards Enoyl Acyl Carrier Protein Reductase Enzyme of Mycrobacterium Leprae

In Silico Design of Dapsone Analogues Effective Towards Enoyl Acyl Carrier Protein Reductase Enzyme of Mycrobacterium Leprae

Authors: Sahu SK, Mohanty P, Banerjee M
Publication: World J Pharm Res
Keywords: Antimalarial agents, chloroquine derivatives, Lactate dehydrogenase
Software: ADMET Predictor®

A series of new antileprotic drugs targeting enoyl acyl carrier protein reductase (ENR) enzyme of Mycobacterium lepraewere designed by in silico techniques.

Insights into DPI sensitivity to humidity: An integrated in-vitro-in-silico risk-assessment

Insights into DPI sensitivity to humidity: An integrated in-vitro-in-silico risk-assessment

Authors: Radivojev S, Pinto JT, Fröhlich E, Paudel A
Publication: J Drug Deliv Sci Technol
Keywords: dry powder inhaler (dpi), inhaled drug, lung concentrations, PBPK modeling, pulmonary absorption model
Software: GastroPlus®

Dry powder inhalers (DPIs) are known to be sensitive to humidity. Erroneous storage of these products by patients in high humidity environments, could present a potential risk.

Toward the establishment of a standardized pre-clinical porcine model to predict food effects – Case studies on fenofibrate and paracetamol

Toward the establishment of a standardized pre-clinical porcine model to predict food effects – Case studies on fenofibrate and paracetamol

Authors: Henze LJ, Koehl NJ, O’Shea JP, Holm R, Vertzoni M, Griffin BT
Publication: Int J Pharm
Keywords: compartmental pk, food effect, gastric emptying, nca, noncompartmental analysis (NCA)
Software: GastroPlus®, PKPlus™

A preclinical porcine model that reliably predicts human food effect of fenofibrate was developed. Fenofibrate was administered to pigs as model compound with a positive food effect.

Exposure-response (E-R) analysis of efficacy of pegvorhyaluronidase alfa (PEGPH20) in combination with nab-paclitaxel + gemcitabine (AG) in patients (Pts) with metastatic pancreatic ductal adenocarcinoma

Exposure-response (E-R) analysis of efficacy of pegvorhyaluronidase alfa (PEGPH20) in combination with nab-paclitaxel + gemcitabine (AG) in patients (Pts) with metastatic pancreatic ductal adenocarcinoma

Authors: Liu Y, Bullock AJ, Passarell JA, Bihorel S, Fiedler-Kelly J, Heineman TC, Sekulovich RE
Publication: Journal of Clinical Oncology
Keywords: metastatic pancreatic ductal adenocarcinoma, PEGPH20, tumor biopsy
Division: Clinical Pharmacology and Pharmacometrics (CPP)

PEGPH20 depolymerizes extracellular matrix hyaluronan (HA) and is an investigational agent for the treatment of pts with HA-accumulating tumors

Solidified SNEDDS for the oral delivery of rifampicin: Evaluation, proof of concept, in vivo kinetics, and in silico GastroPlusTM simulation

Solidified SNEDDS for the oral delivery of rifampicin: Evaluation, proof of concept, in vivo kinetics, and in silico GastroPlusTM simulation

Authors: Hussain A, Shakeel F, Singh SK, Alsarra IA, Faruk A, Alanazi FK, Peter Christoper GV
Publication: Int J Pharm
Keywords: enabled formulations, IVIVC, mechanistic absorption model, PBPK modeling
Software: ADMET Predictor®, GastroPlus®

The present investigation was performed to develop a rifampicin (RIF)-loaded solidified self-nanoemulsifying drug delivery system (SNEDDS) (solidified RIF-OF1) for in vitro and in vivo evaluations.

Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy

Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy

Authors: Conrado DJ, Larkindale J, Berg A, Hill M, Burton J, Abrams KR, Abresch RT, Bronson A, Chapman D, Crowther M, Duong T, Gordish-Dressman H, Harnisch L, Henricson E, Kim S, McDonald CM, Schmidt S, Vong C, Wang X, Wong BL, Yong F, Romero K
Publication: J Pharmacokinet Pharmacodyn
Keywords: cognigen consulting, drug development tools, duchenne muscular dystrophy consortium (D-RSC), model-informed drug development, rare diseases, regulatory endorsement

Drug development for rare diseases is challenged by small populations and limited data.