pevonedistat + rifampin

Pevonedistat + rifampin refers to a drug regimen in which the investigational small molecule **pevonedistat**, a selective inhibitor of the NEDD8-activating enzyme (NAE), is administered alongside **rifampin**, a well-established antibiotic and strong inducer of CYP3A metabolic enzymes. Pevonedistat inhibits NAE, thereby disrupting neddylation, leading to accumulation of specific CRL substrate proteins, proteotoxic stress, and apoptosis in malignant cells. This regimen has been studied specifically to assess how rifampin affects the pharmacokinetics of pevonedistat in patients with advanced solid tumors. Rifampin induces CYP3A, which can accelerate pevonedistat metabolism, but coadministration has been shown to reduce pevonedistat systemic exposure by ~20%, a change considered clinically insignificant in context of inter-patient variability[1][3][5]. Pevonedistat is primarily under development for treatment of myelodysplastic syndromes, acute myeloid leukemia, and other advanced malignancies; rifampin is used here as a pharmacokinetic modulator, not for its antimicrobial effects.