Single and multiple dose intravenous and oral pharmacokinetics of the hedgehog pathway inhibitor vismodegib in healthy female subjects

• Published in: British journal of clinical pharmacology Vol. 74; no. 5; pp. 788 - 796
• Main Authors: Graham, Richard A., Hop, Cornelis E. C. A., Borin, Marie T., Lum, Bert L., Colburn, Dawn, Chang, Ilsung, Shin, Young G., Malhi, Vikram, Low, Jennifer A., Dresser, Mark J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2012; Blackwell; Blackwell Science Inc
• Subjects: absolute bioavailability; Anilides - administration & dosage; Anilides - pharmacokinetics; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Biological Availability; Blood Proteins - metabolism; Chromatography, Liquid; clearance; Drug Administration Schedule; Female; GDC‐0449; Half-Life; Humans; Injections, Intravenous; Mass Spectrometry - methods; Medical sciences; Middle Aged; Nonlinear Dynamics; of distribution; Pharmacokinetics; Pharmacology. Drug treatments; Protein Binding; Pyridines - administration & dosage; Pyridines - pharmacokinetics; Solubility; Tandem Mass Spectrometry; Tissue Distribution; vismodegib; volume; Human; Intravenous administration; Healthy subject; Single dose; Oral administration; of distribution; vismodegib; Bioavailability; Clearance; Multiple dose; GDC-0449; volume; Hedgehog protein; absolute bioavailability; Distribution; Inhibitor; Pharmacokinetics

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • While recent publications have suggested the pharmacokinetics (PK) of vismodegib appear to be non‐linear, there has not been a report describing the mechanisms of non‐linearity. WHAT THIS STUDY ADDS • This study provides evidence that two separate processes...