化合物详情

The purpose of this investigation was to evaluate the ability of the cysteinyl-rich protein metallothionein (MT) to protect cells against the cytotoxic effects of prednimustine, an ester of chlorambucil & prednisolone. The cells studied were MT-rich substrains of murine fibroblasts (C1 1D100) & human epithelial cells (HE100), both demonstrated in an earlier report to exhibit an approx 3-fold incr in resistance to chlorambucil compared to their parent lines (C1 1D & HE) ... . Both in cloning & in growth rate studies the MT-rich strains proved to be significantly more resistant also to prednimustine. E.g. in cloning studies D0 for C1 1D cells (D0= the dose of drug reducing survival to 1/e) was 8.7 ug/ml prednimustine, whereas D0 for C1 1D100 was 12.4 ug/ml, representing an approx 1.5-fold...

IARC Monographs: Volume 50: (1990) Pharmaceutical Drugs

In the rat prednimustine, the prednisolone ester of chlorambucil, is much less toxic than equimolar doses of chlorambucil, when administered subcutaneously (SC). This is due to differences in alkylating agent pharmacokinetics. Prednimustine injected SC produced low plasma concns (<5 microM) of the alkylating metabolites chlorambucil & phenyl acetic mustard, which were maintained for 48 hr. No unhydrolysed prednimustine could be detected. Chlorambucil, in contrast, was rapidly absorbed, peak levels (40 microM) occurring within 2 hr, after which chlorambucil & phenyl acetic mustard plasma levels decreased with half-lives of 2.4 hr & 2.9 hr respectively. The toxicity of chlorambucil could be similarly reduced by administering either the methyl ester of chlorambucil or by giving chlorambuci...

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/