Bortezomib Administration With Severe Hyperbilirubinemia Caused by Hepatic Plasma Cell Infiltration: A Case Report

Introduction Bortezomib, a first-in-class selective and reversible 26S proteasome inhibitor, has been available for use in patients with newly diagnosed and relapsed/refractory multiple myeloma since US Food and Drug Administration approval in May 2003. The clinical pharmacology and metabolic fate of bortezomib after administration has been well described, with hepatic clearance by oxidative deboronation by the cytochrome P450 (CYP) 3A4 and CYP2C19 pathways accounting for the majority of elimination. Bortezomib and its major inactive metabolites do not significantly inhibit hepatic CYP pathways but are subject to increased exposure with concurrent strong CYP3A4 inhibitors. Bortezomib clearance decreases with repeated dosing, leading to increasing exposure over multiple cycles. Additionally, cases of bortezomib-induced hepatic dysfunction have