Concentration-QTc Analysis of Quizartinib in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Concentration-QTc Analysis of Quizartinib in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Publication: Cancer Chemother Pharmacol

This analysis evaluated the relationship between concentrations of quizartinib and its active metabolite AC886 and QT interval corrected using Fridericia's formula (QTcF) in patients with...

Quantitative systems toxicology (QST) to investigate mechanisms contributing to clinical bilirubin elevations

Quantitative systems toxicology (QST) to investigate mechanisms contributing to clinical bilirubin elevations

Conference: AASLD
Software: DILIsym®

To be presented at the FDA/CDER and AASLD 2021 DILI Conference XVIII. Quantitative systems toxicology (QST) to investigate mechanisms contributing to clinical bilirubin elevations: Some patients treated with Drug X experienced clinically relevant elevations in serum bilirubin with concomitant ALT elevations, indicative of potentially severe liver injury (Hy’s Law cases). However, the interpretation is complicated if there is evidence that a compound directly alters bilirubin disposition, leading to bilirubin elevations absent liver injury. Distinguishing between these two possibilities is critical to inform drug development decisions. DILIsym, a QST platform of drug-induced liver injury (DILI), was used to investigate the interpretation of putative Drug X-related elevations in liver biomarkers.

Assessing the Potential for Hepatotoxicity for Combination Therapy of Valproate (VPA) and (CBD) using Quantitative Systems Toxicology (QST)

Assessing the Potential for Hepatotoxicity for Combination Therapy of Valproate (VPA) and (CBD) using Quantitative Systems Toxicology (QST)

Conference: AASLD
Software: DILIsym®

To be presented at the FDA/CDER and AASLD 2021 DILI Conference XVIII. Assessing the Potential for Hepatotoxicity for Combination Therapy of Valproate (VPA) and (CBD) using Quantitative Systems Toxicology (QST). We aimed to identify the mechanism(s) accounting for the higher incidence of ALT elevation observed in individuals treated with VPA and CBD by using a Quantitative Systems Toxicology (QST) model of hepatotoxicity (DILIsym®) to test the hypothesis that increased incidence of ALT elevation was due to VPA and CBD (or metabolites of each) inhibiting mitochondrial respiration.

Molecular modeling for potential cathepsin L inhibitor identification as new anti-photoaging agents from tropical medicinal plants

Molecular modeling for potential cathepsin L inhibitor identification as new anti-photoaging agents from tropical medicinal plants

Publication: J Bioenerg Biomemb
Software: ADMET Predictor®

Ultraviolet exposure can cause photoaging toward the human skin which is begun by the inflammation on the exposure area, also resulting in activation of a degradative enzyme cathepsin L.

Prediction of fraction unbound in plasma in children in data-limited scenarios for human health risk assessment

Prediction of fraction unbound in plasma in children in data-limited scenarios for human health risk assessment

Authors: Yun YE, Edginton AN
Publication: Computational Toxicology
Software: ADMET Predictor®

In human health risk assessment, pediatric physiologically-based pharmacokinetic modeling has been used to predict chemical-specific toxicokinetic adjustment factors.

A Phase 1b Study of Oral Chk1 Inhibitor LY2880070 as Monotherapy in Patients with Advanced or Metastatic Cancer

A Phase 1b Study of Oral Chk1 Inhibitor LY2880070 as Monotherapy in Patients with Advanced or Metastatic Cancer

Publication: ASCO

In the context of DNA damage, Checkpoint Kinase 1 (Chk1) mediates a checkpoint response which arrests the cell cycle and allows the cell to complete DNA repair and replication.

Experimental Solubility, Thermodynamic/Computational Validations, and GastroPlus-Based In Silico Prediction for Subcutaneous Delivery of Rifampicin

Experimental Solubility, Thermodynamic/Computational Validations, and GastroPlus-Based In Silico Prediction for Subcutaneous Delivery of Rifampicin

Publication: AAPS PharmSciTech
Software: GastroPlus®

We focused to explore a suitable solvent for rifampicin (RIF) recommended for subcutaneous (sub-Q) delivery [ethylene glycol (EG), propylene glycol...

Extemporaneous Compounding and Physiological Modeling of Amlodipine/Valsartan Suspension

Extemporaneous Compounding and Physiological Modeling of Amlodipine/Valsartan Suspension

Publication: Int J Hypertension
Software: GastroPlus®
Division: PBPK

In case of absent liquid dosage form, crushing a tablet or dispersing a capsule would be the most convenient option for using these drugs in patients with dysphagia difficulties.