Potential CYP3A-mediated drug-drug interactions and excretion of the antibody drug conjugate brentuximab vedotin in patients with hematologic malignancies that are CD30-positive

• Hong kong

  English

  Author

An antibody-drug conjugate (ADC) called benuximab vedotin preferentially transports 
monomethyl auristatin E (MMAE) into cells that express CD30. This study assessed the excretion 
of MMAE and the possibility for CYP3A-mediated drug-drug interactions with brentuximab 
vedotin. 56 patients with CD30-positive hematologic malignancies received two 21-day cycles of 
intravenous brentuximab vedotin (1.2 or 1.8 mg/kg). Additionally, each patient was given either a 
potent inhibitor (ketoconazole), an efficient inducer (rifampin), or a sensitive CYP3A substrate 
(midazolam). Midazolam exposures were unaffected by benuximab vedotin. Concomitant 
rifampin or ketoconazole had no effect on ADC exposures, however MMAE exposures were 
reduced with 

• pdf