gdc-0152 and Hemolysis

gdc-0152 has been researched along with Hemolysis* in 1 studies

Other Studies

1 other study(ies) available for gdc-0152 and Hemolysis

ArticleYear
Cyclodextrin Reduces Intravenous Toxicity of a Model Compound.
    Journal of pharmaceutical sciences, 2019, Volume: 108, Issue:6

    Solubilization of new chemical entities for toxicity assessment must use excipients that do not negatively impact drug pharmacokinetics and toxicology. In this study, we investigated the tolerability of a model freebase compound, GDC-0152, solubilized by pH adjustment with succinic acid and complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) to enable intravenous use. Solubility, critical micelle concentration, and association constant with HP-β-CD were determined. Blood compatibility and potential for hemolysis were assessed in vitro. Local tolerability was assessed after intravenous and subcutaneous injections in rats. A pharmacokinetic study was conducted in rats after intravenous bolus administration. GDC-0152 exhibited pH-dependent solubility that was influenced by self-association. The presence of succinic acid increased solubility in a concentration-dependent manner. HP-β-CD alone also increased solubility, but the extent of solubility enhancement was significantly lower than succinic acid alone. Inclusion of HP-β-CD in the solution of GDC-0152 improved blood compatibility, reduced hemolytic potential by ∼20-fold in vitro, and increased the maximum tolerated dose to 80 mg/kg.

    Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Cyclohexanes; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Interactions; Excipients; Hemolysis; Injections, Intravenous; Injections, Subcutaneous; Male; Maximum Tolerated Dose; Models, Animal; Pyrroles; Rats; Solubility; Toxicity Tests, Acute

2019