A clinical drug–drug interaction study to evaluate the effect of a proton-pump inhibitor, a combined P-glycoprotein/cytochrome 450 enzyme (CYP)3A4 inhibitor, and a CYP2C9 inhibitor on the pharmacokinetics of vismodegib

• Published in: Cancer chemotherapy and pharmacology Vol. 78; no. 1; pp. 41 - 49
• Main Authors: Malhi, Vikram, Colburn, Dawn, Williams, Sarah J., Hop, Cornelis E. C. A., Dresser, Mark J., Chandra, Priya, Graham, Richard A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2016; Springer Nature B.V
• Subjects: Anilides - administration & dosage; Anilides - pharmacokinetics; Area Under Curve; ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Cancer Research; confidence interval; cytochrome P-450; Cytochrome P-450 CYP2C9 Inhibitors - administration & dosage; Cytochrome P-450 CYP2C9 Inhibitors - pharmacology; Cytochrome P-450 CYP3A Inhibitors - administration & dosage; Cytochrome P-450 CYP3A Inhibitors - pharmacology; Drug Interactions; enzymes; Erinaceidae; Female; fluconazole; Fluconazole - administration & dosage; Fluconazole - pharmacology; Humans; Hydrogen-Ion Concentration; itraconazole; Itraconazole - administration & dosage; Itraconazole - pharmacology; Medicine; Medicine & Public Health; Oncology; Original; Original Article; P-glycoproteins; pharmacokinetics; Pharmacology/Toxicology; proton pump; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - pharmacology; Pyridines - administration & dosage; Pyridines - pharmacokinetics; Rabeprazole - administration & dosage; Rabeprazole - pharmacology; risk; Solubility; Clinical pharmacology; CYP inhibitors; Clinical drug–drug interaction; Pharmacokinetic; Proton-pump inhibitor; P-glycoprotein inhibitor
• ISSN: 0344-5704; 1432-0843; 1432-0843
• DOI: 10.1007/s00280-016-3020-z

Purpose The Hedgehog pathway inhibitor vismodegib exhibits pH-dependent solubility, and in vitro studies have shown that vismodegib is a substrate of P-glycoprotein (P-gp) and is metabolized by cytochrome P450 (CYP) 2C9 and 3A4. The objective of this four-arm parallel study in healthy subjects was t...