化合物详情

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), bendamustine, which has an estimated vapor pressure of 1.3X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase Bendamustine may be removed from the air by wet or dry deposition(SRC). Bendamustine does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of bendamustine can be estimated to be 5200(SRC). According to a classification scheme(2), this estimated Koc value suggests that bendamustine is expected to be immobile in soil. Bendamustine is a zwitterion with cationic tendencies at environmental pH values of 5 to 9(3).

An estimated BCF of 3 was calculated in fish for bendamustine(SRC), using an estimated log Kow of 4.23(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for bendamustine is estimated as 3.9X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that bendamustine is expected to be essentially nonvolatile from water surfaces(2). Bendamustine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.3X10-11 mm Hg(SRC), determined from a fragment constant method(3).

The rate constant for the vapor-phase reaction of bendamustine with photochemically-produced hydroxyl radicals has been estimated as 2.1X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.8 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Bendamustine is an alkylating agent that may hydrolyze under environmental conditions(2). Bendamustine does not contain chromophores that absorb at wavelengths >290 nm(2) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

While data specific to bendamustine were not located(SRC, 2009), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Bendamustine's production and use as a medication to treat chronic lymphocytic leukemia(1) may result in its release to the environment through various waste streams(SRC).

Occupational exposure to bendamustine may occur through dermal contact with this compound at workplaces where bendamustine is produced or used. General population exposure may be limited to those administered bendamustine via its use as a medication. (SRC)

Bendamustine's production and use as a medication to treat chronic lymphacytic leukemia may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.3X10-11 mm Hg at 25 °C indicates bendamustine will exist solely in the particulate phase in the atmosphere. Particulate-phase bendamustine will be removed from the atmosphere by wet or dry deposition. Bendamustine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, bendamustine is expected to have no mobility based upon an estimated Koc of 5200. Bendamustine is a zwitterion with cationic tendencies at environmental pH values of 5 to 9. Volatilization from mois...

Likelihood score: C (probable cause of clinically apparent liver injury, some of which is due to reactivation of hepatitis B).

/SIGNS AND SYMPTOMS/ Infections, including pneumonia and sepsis, have been reported in patients receiving bendamustine and have been associated with hospitalization, septic shock, and death. Patients with myelosuppression have increased susceptibility to infection and should be advised to contact their clinician if signs or symptoms of infection occur.

References: DOI:10.1016/j.drudis.2019.09.022

LD50 Mouse iv 80 mg/kg /Bendamustine hydrochloride/[The Merck Index, Fourteenth Edition (2006)

/GENOTOXICITY/ Bendamustine is a mutagen and clastogen. In a reverse bacterial mutation assay (Ames assay), bendamustine was shown to increase revertant frequency in the absence and presence of metabolic activation. Bendamustine was clastogenic ... in rat bone marrow cells in vivo (increase in micronucleated polychromatic erythrocytes) from 37.5 mg/sq m, the lowest dose tested.

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use...

Some evidence indicates that the closely related drug carmustine can increase serum prolactin.