Population Pharmacokinetics of Bendamustine and Metabolites in Patients With Indolent Non-Hodgkin Lymphoma

Authors: Owen JS, Melhem M, D’Andrea D, Darwish M
Conference: ASCPT
Keywords: alkylating agent, antineoplastics, body surface area, BSA, cancer, dose proportionality, intravenous, IV, metabolites, NONMEM, Oncology, PK
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

  • Bendamustine is a bifunctional alkylating agent in development as monotherapy and in combination with other agents in the treatment of indolent non-Hodgkin lymphoma (NHL):
    • Synthesized to combine the act ivi t ies of a purine antimetabolite (benzimidazole) with the a lkyl a t ing prope r t i e s of the bi func t iona l mechlorethamine nitrogen mustard1,2
    • Converted in vivo to active metabolites: γ-hydroxy bendamustine (M3) and N-desmethyl bendamustine (M4)
  • The precise mechanism of action of bendamustine in humans has not been fully characterized, although it differs from other alkylating agents.

American Society for Clinical Pharmacology and Therapeutics (ASCPT); Orlando, Florida; April 2008

By Joel S. Owen, M. Melhem, D. D’Andrea, M. Darwish