Metabolism of cyclophosphamide.
N. Brock,H.-J. Hohorst +1 more
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The authors conclude that the greater specificity of Endoxan as compared to other cytostatic agents of the N‐mustard group may be due to some specific permeation properties of the primary alkylating metabolite of Endxan rather than to a possible specific mechanism of action of this compound within tumor cells.Abstract:
The in vivo activation of cyclophosphamide (Endoxan) to cytostatic and alkylating metabolites has been studied. Endoxan is metabolized to the weak anion by microsomal dealkylation in the rat's liver; this product is the first alkylating metabolite. About 80% of the alkylating activity of the serum, occurring 30 min after injection of Endoxan is presented by this primary alkylating metabolite. Nor-N-mustard and N-2-chloroethyl-aziridine were found only in traces. Although some activation was detected in the liver, the lungs and to a minor extent the kidneys, this phenomenon has not been detected in the screened experimental rat tumors. The authors conclude that the greater specificity of Endoxan as compared to other cytostatic agents of the N-mustard group may be due to some specific permeation properties of the primary alkylating metabolite of Endoxan rather than to a possible specific mechanism of action of this compound within tumor cells.read more
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Rationale for Design of Biologically Reversible Drug Derivatives: Prodrugs
A.A. Sinkula,Samuel H. Yalkowsky +1 more
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Teratogenic bioactivation of cyclophosphamide in vitro.
TL;DR: These experiments represent the first direct demonstration of bioactivation of a proteratogen in vitro and show that cyclophosphamide concentrations as high as 250 micrograms per milliliter were innocuous when either the microsomal material or cofactors were omitted from the medium.
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Enzymatic Metabolism of Cyclophosphamide and Nicotine and Production of a Toxic Cyclophosphamide Metabolite
TL;DR: Carboxyphosphamide, which has little or no antitumor effect, is much less toxic to clone formation of human epidermoid carcinoma No. 2 cells and to L1210 cells, and administration of pyridoxal in combination with cyclophosphamide increases the life-span of mice implanted with L 1210 cells.
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Urological Complications of Cyclophosphamide
TL;DR: An Article de synthese sur la toxicite de the cyclophosphamide et sur les preventions et traitements possibles de ces complications.
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