Drugs chlorambucil

Davies, I.D., Allanson, J.P., and Causon, R.C. 1999. Rapid determination of the anti-cancer drug chlorambucil (Leukeran) and its phenyl acetic acid mustard metabolite in human serum and plasma by automated solid-phase extraction and liquid chromatography-tandem mass spectrometry. J. Chrom-matogr. B. 732 173. 

Kratz F, Beyer U, Roth T, Schulte MT, Unold A, Fiebig HH, Unger C (1998) Albumin conjugates of the anticancer drug chlorambucil synthesis, characterization, and in vitro efficacy. Arch Pharm (Weinheim) 331 47-53... 

Significant improvements were achieved with the drugs chlorambucil (Leukeran, 1952) and melphalan (Alkeran, 1954), both developed at the Chester Beatty Laboratory in London. These drugs were more water-soluble (and hence available by mouth rather than intravenous infusion) and more easily taken up by cancer cells. They were also less toxic to bone-marrow cells and have been widely used over the intervening years for the treatment of various leukaemias and other tumours. An interesting combination of the female sex hormone oestradiol with mechlorethamine was invented in Romania in 1966, and was marketed under the trade-name Estracyte (estra-mustine) for the treatment of prostatic cancer. 

Synthesis and biophysical characterization of four prodrug ether phospholipid conjugates (29-32) have been described by Clausen and co-workers. " The lipids were prepared from the anticancer drug chlorambucil and had Cl6 and Cl8 ether chains with phosphatidylcholine or phosphati-dylglycerol headgroups. All four prodrugs possessed the ability to form unilamellar liposomes (86-125 nm) that were hydrolyzed by phospholipase A2 resulting in chlorambucil release. 

Many drugs have been conjugated to antibodies or their fragments, including daunomycin [113], cyclosporine [114], platinum [115], chlorambucil [116], and vindesine [117], When choosing a drug for this type of... 

Most warn of the increased risk of deformities of limb development and defects like cleft palate. A few drugs carry the risk of distinct organ defects. For example, chlorambucil may cause agenesis of the fetal kidneys Penicillamine seems to affect fetal connective tissue, causing relaxation of the skin, hypotonia, and hyper flexion of the hips and shoulders... 

J. Hovinen, R. Silvennoinen, J. Vilpo, Detoxification of an Alkylating Drug, (V,(V-Bis(2-chloroethyl)-P-aminophenylbutyric Acid (Chlorambucil), in Human Gastric Juice and Saliva , Chem. Res. Toxicol. 1998, 11, 91 - 93. 

Chlorambucil is well adsorbed when administered orally. It is used for chronic lymphatic leukemia and for multiple myelomas. Synonyms of this drug are leukeran, amboclorin, and others. 

Melphalan Melphalan, L-3-[p-[bis-(2-chloroethyl)amino]phenyl]alanine (30.2.1.13), is a structural analog of chlorambucil in which the butyric acid fragment is replaced with an aminoacid fragment, alanine. This drug is synthesized from L-phenylalanine, the nitration of... 

FIGURE 6.6 A triglyceride derivative of chlorambucil, where the chlorambucil attached to the 2-position, and palmitic acid to positions 1 and 3 of the triglyceride. (From Stella, VJ. and Pochopin, N.L. Lymphatic Transport of Drugs, Charman, W.N. and Stella, V.J., Eds., CRC Press, Boca Raton, 1992, p. 181. With permission.)... 

Chlorambucil is an anticancer chemotherapeutic agent, used in the treatment of lymphomas. The targeting of this drug to the lymphatic system may improve the treatment of lymphatic cancers. Hence, a prodrug of chlorambucil was synthesized, with the parent drug attached to the 2-position of a triglyceride with palmitic acid in the 1 and 3 positions (Figure 6.6). 

A variety of other agents with cytotoxic effects has been used to suppress the immune system. These drugs include chlorambucil (Leukeran), dactinomycin (Cosmegen), mercaptopurine (Purinethol), vinblastine (Velban), and vincristine (Oncovin, Vincasar).41 These... 

Chlorambucil (Leukeran) is the least toxic nitrogen mustard, and is used as the drug of choice in the treatment of chronic lymphocytic leukemia. It is absorbed orally, is slow in its onset of action, and may cause bone marrow depression. 

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