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Metabolic stability of proteasome inhibitors and midazolam using pooled human liver microsomes. The metabolism of MG-132 (A), epoxomicin (B), and bortezomib (C) by HLM were monitored by a substrate depletion method. Aliquots were taken from the incubation mixtures at 0, 5, 10, 15, 20, and 30 min, and the quenched samples were analyzed by LC-MS/MS. Ketoconazole (1 μM) was used as a competitive inhibitor of CYP3A4.
