Bendamustine

Absorption

Following a single IV dose of bendamustine hydrochloride Cmax typically occurred at the end of infusion. The dose proportionality of bendamustine has not been studied.

Toxicity

Risk for tumor-lysis syndrome. Discontinue use in the event of severe/progressive skin reactions. Hematologic malignancies of different forms reported. Discontinue use in the case of severe infusion reactions. May cause extravasation. Mild to moderate renal impairment. Mild hepatic impairment. Sepsis (infections) may occur. Avoid use if pregnant. Possibility of anaphylaxis or infusion reactions- severe in rare cases.

The Uses of Bendamustine

Treatment of hematologic cancer, especially non-Hodgkin’s lymphoma.

Indications

Bendamustine is indicated for use in the treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

Background

Bendamustine is a nitrogen mustard drug indicated for use in the treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Bendamustine is a bifunctional mechlorethamine derivative capable of forming electrophilic alkyl groups that covalently bond to other molecules. Through this function as an alkylating agent, bendamustine causes intra- and inter-strand crosslinks between DNA bases resulting in cell death. It is active against both active and quiescent cells, although the exact mechanism of action is unknown.

Definition

ChEBI: Bendamustine is a member of benzimidazoles.

brand name

Ribomustine (Amcis AG, Switzerland).

Pharmacokinetics

No mean changes in QTc interval greater than 20 milliseconds were detected up to one hour post-infusion.

Enzyme inhibitor

This nitrogen mustard and anticancer drug (FWfree-acid = 358.26 g/mol; CAS 16506-27-7), also known by its code name SDX-105, its trade names Treanda?, Treakisym?, Ribomustin?, and Levact?, as well as by its systematic name 4-[5-[bis(2-chloroethyl)amino]-1-methylbenzimidazol-2- yl]butanoic acid, is a relatively nonspecific DNA alkylating agent that causes intra- and inter-strand cross-links. Bendamustine is used in the treatment of chronic lymphocytic leukemia (CLL), Hodgkin’s disease, nonHodgkin’s lymphoma, multiple myeloma and lung cancer. Pharmacokinetics: After intravenous infusion, >95% of the drug becomes protein-bound, mainly to albumin; however, only free bendamustine is active. Bendamustine is metabolized by liver cytochrome p450, and elimination (renal) is biphasic, with an initial half-life of 6–10 minutes and a terminal half-life of approximately 30 minutes.

Metabolism

In vitro data indicate that bendamustine is primarily metabolized via hydrolysis to monohydroxy (HP1) and dihydroxy-bendamustine (HP2) metabolites with low cytotoxic activity. Two active minor metabolites, M3 and M4, are primarily formed via CYP1A2. However, concentrations of these metabolites in plasma are 1/10th and 1/100th that of the parent compound, respectively, suggesting that the cytotoxic activity is primarily due to bendamustine. Results of a human mass balance study confirm that bendamustine is extensively metabolized via hydrolytic, oxidative, and conjugative pathways.