TY - JOUR
T1 - Metabolism and mechanisms of action of bendamustine
T2 - Rationales for combination therapies
AU - Gandhi, Varsha
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - Bendamustine hydrochloride is the active ingredient of Ribomustin (Ribosepharm GmbH, Munich, Germany). It was first synthesized in 1963 in the German Democratic Republic. Bendamustine is chemically related to the alkylating agent chlorambucil, with the benzene ring in the chlorambucil molecule replaced by a I-methyl-benzimidazole moiety. The mechanisms of action of bendamustine have been under investigation since the early 1960s, and its first use was as a treatment for multiple myeloma in 1969. Bendamustine has three active moieties: an alkylating group, in common with the nitrogen mustard family; a benzimidazole ring, which may act as a purine analog; and a butyric acid side-chain. Bendamustine undergoes extensive first-pass metabolism. However, unmetabolized bendamustine accounts for about 45% of the total drug recovered in urine. The main transformation product is a cytotoxic hydroxy metabolite (β-hydroxybendamustine). Bendamustine was originally synthesized with the intention of producing an antineoplastic agent with low toxicity and both alkylating and antimetabolic properties. However, it has been shown that, at least at high concentrations, it acts primarily as an alkylating agent. Based on the multiple actions and cell cycle effects of this agent, mechanism-based combination strategies have been suggested. The rationales behind bendamustine combination regimens and the importance of the sequence of administration of different drugs are explored.
AB - Bendamustine hydrochloride is the active ingredient of Ribomustin (Ribosepharm GmbH, Munich, Germany). It was first synthesized in 1963 in the German Democratic Republic. Bendamustine is chemically related to the alkylating agent chlorambucil, with the benzene ring in the chlorambucil molecule replaced by a I-methyl-benzimidazole moiety. The mechanisms of action of bendamustine have been under investigation since the early 1960s, and its first use was as a treatment for multiple myeloma in 1969. Bendamustine has three active moieties: an alkylating group, in common with the nitrogen mustard family; a benzimidazole ring, which may act as a purine analog; and a butyric acid side-chain. Bendamustine undergoes extensive first-pass metabolism. However, unmetabolized bendamustine accounts for about 45% of the total drug recovered in urine. The main transformation product is a cytotoxic hydroxy metabolite (β-hydroxybendamustine). Bendamustine was originally synthesized with the intention of producing an antineoplastic agent with low toxicity and both alkylating and antimetabolic properties. However, it has been shown that, at least at high concentrations, it acts primarily as an alkylating agent. Based on the multiple actions and cell cycle effects of this agent, mechanism-based combination strategies have been suggested. The rationales behind bendamustine combination regimens and the importance of the sequence of administration of different drugs are explored.
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U2 - 10.1016/s0093-7754(02)90007-2
DO - 10.1016/s0093-7754(02)90007-2
M3 - Review article
C2 - 12170425
AN - SCOPUS:0036340122
SN - 0093-7754
VL - 29
SP - 4
EP - 11
JO - Seminars in oncology
JF - Seminars in oncology
IS - 4 SUPPL. 13
ER -