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

摘要

PurposeThe 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 to evaluate the effect of the proton-pump inhibitor rabeprazole, the P-gp/CYP3A4 inhibitor itraconazole, and the CYP2C9 and 3A4 inhibitor fluconazole on vismodegib steady-state pharmacokinetics.