Cytoxan tablets cyclophosphamide tablets, usp are for oral use and contain 25 mg or 50 mg cyclophosphamide anhydrous. With recent findings concerning their basic and clinical pharmacology, the therapeutic index of. Jan 29, 2020 to raise the efficacy and the selectivity of known medicinal substances ms, methods have recently been developed to create systems for their directed transport in the body using various carriers. Cyclophosphamide is an alkylating agent used in the treatment of several forms of cancer including leukemias, lymphomas and breast cancer. Synthesis and antioxidant activity of dioxazaphosphinin2ones 18 different antioxidant parameters, like the antioxidative enzymes including superoxide dismutase, glutathione peroxidase and catalase cat are commonly used to assess exposure to ros in living cells. Synthesis and antitumor activity of cyclophosphamide analogues. The problem of decreasing the toxicity and increasing the selectivity of antitumor mss is particularly relevant. Preparation, kinetic studies, and anticancer screening of phenylketophosphamide and similar compounds related to the cyclophosphamide metabolite aldophosphamide. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer, small cell lung cancer, neuroblastoma, and sarcoma. Citeseerx document details isaac councill, lee giles, pradeep teregowda. Harvardmit division of health sciences and technology 151 of. Cytoxan cyclophosphamide for injection, usp cytoxan. Cyclophosphamide is a white crystalline powder with the molecular formula c 7 h 15 cl 2 n 2 o 2 p h 2 o and a molecular weight of 279. Cyclophosphamide cp, a prodrug that is enzymatically converted to the cytotoxic 4hydroxycyclophosphamide 4ohcp by hepatic enzymes, is commonly used in both human and veterinary medicine to treat cancers and modulate the immune system.
Burkitts lymphoma and other nonhodgkins lymphomas bleomycin blm. Sigmaaldrich offers a number of cyclophosphamide products. Other studies 23 showed that multidose treatment of hamsters bearing plasmacytomas with cyclophosphamide 2bis2chloroethylamino2h1,3,2oxazaphosphorinane 2oxide. Phospharamide is the active metabolite that creates crosslinks in the dna. Cyclophosphamide monohydrate cas 6055192 calbiochem empirical formula hill notation. The synthesis, characterization and biological assays of two new rhodium carboxylate sugar derivatives and respective cyclosphosphamide adducts are described.
Efficient and divergent synthesis of cyclophosphamide. The reaction scheme for the synthesis of methadone begins with the alkylation of the anion of diphenylacetonitrile produced by reacting a strong base with diphenylacetonitrile with 1dimethylamino2chloropropane, which produces a mixture of two isomeric nitriles, one highmelting commonly referred to as methadone nitrile, 2,2diphenyl4. In solid samples of cyclophosphamide, heated up to its melting point, the first pathway predominates over the second one. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. Cyclophosphamide is an alkylating cytotoxic drug that is toxic not only to cancer cells but. Abstract the degradation of cyclophosphamide in neutral or slightly acidic aqueous solution starts with an intramolecular alkylation leading to an intermediary bicyclic compound which hydrolyses immediately and exclusively to a ninemembered heterocycle. Effects of nitrogen mustard and cyclophosphamide upon the. A healthcare provider will give you this medication. A portion of this oil was converted to the monohydrate by the. To use cyclophosphamide in a drug delivery system suitable cyclophosphamide derivatives bearing functional groups should be synthesized. Cytoxan cyclophosphamide for injection, usp cytoxan tablets. In recent years, studies are underway for the development of conjugates of mss.
An activated form of cyclophosphamide, phosphoramide mustard, alkylates, or binds, to dna. Interferes with dna replication and rna transcription, ultimately disrupting protein synthesis cellcycle phasenonspecific. During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis to reduce the risk of urinary tract. Interleukin 2 il2 activity, natural killer cell nkc cytotoxicity, and serum antibody ab levels were assessed in rats. Formation of cyclophosphamide s active metabolite occurs mainly in the liver. Cyclophosphamide, although effective alone in susceptible malignancies, is more frequently used concurrently or sequentially with other antineoplastic drugs. Cyclophosphamide is well absorbed following an oral dose with a mean halflife of 48 hours for both oral and parenteral administration.
Synthesis and antitumor activity of cyclophosphamide. These actions do not appear to be cellcycle specific. Pdf efficient and divergent synthesis of cyclophosphamide. Degradation products of cyclophosphamide synthesis and. The purpose of this study was to evaluate the protective effects of sublancin on immunosuppression in cyclophosphamidetreated mice.
Borch rf, canute gw 1991 synthesis and antitumor properties of activated cyclophosphamide analogues. But in such a synthesis the metabolism of the drug must be kept in mind, because the pharmacological activities might be lost by the modification. Cyclophosphamide is a cyclic phosphamide with a bis2chloroethyl group that can be metabolized by cells into phosphoramide mustard which alkylates macromolecules, including dna, and crosslinks the two dna strands. Cyclophosphamide is the generic name of the prescription drug cytoxan, a chemotherapy drug for people with certain cancers. As an immune suppressor it is used in nephrotic syndrome, granulomatosis with polyangiitis, and. An overview of cyclophosphamide and ifosfamide pharmacology. Kinetics of cyclophosphamide metabolism in humans, dogs, cats. Pdf a facile and efficient onepot synthesis of substituted cyclophosphamidic chlorides and their analogues has been developed from readily. A convenient method for the synthesis of cyclophosphamide analogues. Cyclophosphamide same as above breast, ovarian, cll. Cyclophosphamide is commonly used with doxorubicin hydroxydaunorubicin, vincristine oncovin, and prednisone known as the chop regimen, with or without other agents, in the treatment of various types of intermediategrade nonhodgkin lymphoma. Effect of lead, polychlorinated biphenyls, and cyclophosphamide on rat natural killer cells, interleukin 2, and antibody synthesis. Death of rapidly replicating cells, particularly malignant ones. Cyclophosphamide is indicated for the treatment of biopsy proven minimal change nephrotic syndrome in.
Cyclophosphamide cp, also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. Cyclophosphamide is a synthetic antineoplastic drug chemically related to the nitrogen mustards. Cyclophosphamide injection is for intravenous or oral administration. Cyclophosphamide injectable solution is a prescription medication used to treat many types of cancer. Cyclophosphamide is an alkylating agent of the nitrogen mustard. Modified guanines representing o 6 alkylation by the cyclophosphamide metabolites acrolein and chloroacetaldehyde. A convenient method for the synthesis of cyclophosphamide. Its cytotoxic effect is mainly due to crosslinking of strands of dna and rna, and to inhibition of protein synthesis. Cyclophosphamide is an alkylating agent of the nitrogen mustard type. In normal mice, the phagocytic activity of mouse peritoneal macrophages was significantly enhanced by oral. Preparation, kinetic studies, and anticancer screening of.
Synthesis and antioxidant activity of dioxazaphosphinin2ones. Subsequent acidcatalyzed hydrolysis of the pnbond leads to a phosphoric acid monoester. Water soluble cyclophosphamide adducts of rhodiumii keto. Cyclophosphamide is a known teratogen with significant limb abnormalities and cognitive impairment resulting from firsttrimester exposure. Cyclophosphamide has also been used as a single agent in the treatment of lowgrade lymphomas. We investigated the metabolism of cp in humans, dogs, cats, and mice using liver microsomes. This invention discloses a solventfree process for the preparation of cyclophosphamide. The title compounds are characterized by nmr, esiqtof, and.
Its prescribed for nonhodgkin lymphoma, hodgkin lymphoma, multiple. The compounds, characterized by q3c and ih nmr, infrared and uvvisible spectra, presented high water solubility and hydration grades were confirmed given the. Efficient and divergent synthesis of cyclophosphamide analogues from 2arylamino3acetyl5,6dihydro4hpyrans dexuan xiang, a peng huang, b kewei wang, a guangyuan zhou, b yongjiu liang b and dewen dong ab. Ludeman sm, boyd vl, regan jb, gallo ka, zon g, ishii k. Cyclophosphamide therapy is associated with minor transient serum enzyme elevations and has been linked to rare cases of acute liver injury. Kinetics of cyclophosphamide metabolism in humans, dogs. Expired fee related application number us07442,486 inventor abu s.
Synthesis, characterization and in vitro cytostatic assays. Water soluble cyclophosphamide adducts of rhodiumii ketogluconate and glucuronate. With recent findings concerning their basic and clinical pharmacology, the therapeutic index of these compounds can be improved. Us5036060a us07442,486 us44248689a us5036060a us 5036060 a us5036060 a us 5036060a us 44248689 a us44248689 a us 44248689a us 5036060 a us5036060 a us 5036060a authority us united states prior art keywords cyclophosphamide sodium chloride colorless parts month prior art date 19880725 legal status the legal status is an assumption and is not a legal conclusion. Oct 24, 2010 borch rf, canute gw 1991 synthesis and antitumor properties of activated cyclophosphamide analogues. Synthesis of activated cyclophosphamide derivatives. Phosphorus, sulfur, and silicon and the related elements. Prevention of cyclophosphamideinduced immunosuppression. Cytoxan tablets cyclophosphamide tablets, usp are for oral use and contain 25 mg or 50 mg cyclophosphamide. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed. It must be metabolized by the body to convert it in its active metabolite. Harvardmit division of health sciences and technology 151. Synthesis and investigation of the physicochemical properties.
Pdf water soluble cyclophosphamide adducts of rhodiumii. Synthesis and antitumor activity of cyclophosphamide analogs. Synthesis and investigation of the physicochemical. Pdf modified guanines representing o 6 alkylation by the. Maximum inhibition of synthesis did not occur immediately following the administration of the agent but was observable 2448 hours later. Us20140066654a1 solventfree process for the preparation. Synthesis of cyclophosphamide analogs from aminotrideoxy sugars. In recent years, studies are underway for the development of conjugates of mss and. As an immune suppressor it is used in nephrotic syndrome, granulomatosis with polyangiitis. Cyclophosphamide is a component of the chop regimen cyclophosphamide, doxorubicin, vincristine, and prednisone that is commonly used for treating nonhodgkins lymphoma. Mechlorethamine dna crosslinks, resulting in inhibition of dna synthesis and function hodgkins and nonhodgkins lymphoma must be given orally nausea and vomiting, decrease in pbl count, bm depression, bleeding, alopecia, skin pigmentation, pulmonary fibrosis b. An oral preparation may be prepared by dissolving cyclophosphamide for injection in aromatic. Us20140066654a1 solventfree process for the preparation of.
Cyclophosphamide fda prescribing information, side effects. Inhibitors of nucleotide synthesis drug mechanism of action. This inhibition was accompanied by a decrease in dna nucleotidyltransferase activity of. Inhibitors of nucleotide synthesis drug mechanism of. In addition, when given in high doses as a part of a myeloablative. Single doses of nitrogen mustard or cyclophosphamide caused regression of plasmacytomas in hamsters and decreases in the rate of synthesis of dna and rna by the tumors. Cyclophosphamide side effects, warnings, dosage, and more. Efficient and divergent synthesis of cyclophosphamide analogues from 2arylamino3acetyl5,6dihydro4hpyrans dexuan xiang, a peng huang, b kewei wang, a guangyuan zhou. To raise the efficacy and the selectivity of known medicinal substances ms, methods have recently been developed to create systems for their directed transport in the body using various carriers.
Dna and rna, and to inhibition of protein synthesis. Efficient and divergent synthesis of cyclophosphamide analogues from 2arylamino3acetyl5,6dihydro4hpyrans article pdf available in chemical communications january 2009 with 192 reads. Sublancin is a glycosylated antimicrobial peptide produced by bacillus subtilis 168 with combined antibacterial and immunomodulatory activities. A new method for the preparation of ifosfamide and. Cyclophosphamide daviss drug guide for rehabilitation. Formation of cyclophosphamides active metabolite occurs mainly in the liver. Fidanze, in comprehensive medicinal chemistry ii, 2007. Cyclophosphamide does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. The structures of the phosphorus compounds were established by 1h and 31p nmr spectroscopy, and synthesis. According to this invention, there is no solvent used during the reaction step for preparing cyclophosphamide, so that the total volume of the reaction for preparing cyclophosphamide can be reduced and the manufacture of cyclophosphamide can become more efficient. Inactive parent drug is well absorbed from the gi tract.
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