Adriamycin metabolism

We had previously eliminated the possibility that retinol affected bacterial viability in this assay. The likelihood of a non-specific inhibitory effect of retinol was also eliminated, since there was no effect of vitamin A alcohol on mutagenicity induced by adriamycin, a direct-acting mutagen in Salmonella (23). Thus, these findings demonstrated that retinol inhibited the metabolism of 2-fluorenamine by rat liver tissue preparations to forms capable of producing mutations in S typhimurium. 

It has also been demonstrated that PI, whose metabolic turnover generates the important messenger molecules inositol and DAG, is different in adriamycin-sensitive and -resistant cells. The resistant cells show an increased turnover. This could be important for PKC activity, as one of the functions of DAG is the control of PKC activity. Indeed, it has been shown that the activities of PKC in resistant and sensitive cells... 

Matthews, N., Neale, M.L., Jackson, S.K., and Stark, J.M., 1987, Tumor cell killing by tumor necrosis factor inhibition by anearobiotic condition, free-radical scavengers and inhibitors of arachidonate metabolism. Immunology 62 153-155 Miller, M.G., Rodgers, A., and Cohen, G.M., 1986, Mechanisms oftoxicity of naphthoquinones to isolated hepatocytes. Biochem. Pharmacol. 35 1177-1184 Minko, T., Kopeckova, P., and Kopecek, J., 1999, Comparison ofthe anticancer effect of free and HPMA copolymer-bound adriamycin in human ovarian carcinoma cells. Pharmaceut. Res. 16 986-996... 

Another agent which we have used to evaluate the influence of Mn on superoxide metabolism is the antibiotic Adriamycin (ADR). Adriamycin is considered one of the most potent drugs in the field of chemotherapy, yet its clinical usefulness is compromised by a number of serious side effects including a dose-dependent cardio-toxicity. Adriamycin-induced heart disease is characterized by degeneration of the cardiac muscle mitochondria are enlarged and the intracristal spaces are substantially extended. 

Paracetamol, adriamycin, quinones, nitrosamines, aromatic amines, halothane etc. form free-radical intermediates by metabolic activation in the liver.)... 

Eventually these reactions result in the oxidative destruction of cellular membrane and serious tissue damage in the liver even though <0.5% of CCI4 is ever metabolized. An essential involvement of lipid peroxidation in the events leading to death of hepatocytes has been proved in the acute intoxication as well as with other haloalkanes such as bromotrichloromethane (CBrCls), dibromoethane, and halothane. Lipid peroxidation is also involved in the hepatotoxicity of ethanol, allyl alcohol, and some drugs like adriamycin. 

Zidovudine is rapidly absorbed from the G1 tract with peak serum concentrations occurring within 30 to 90 minutes. It binds to plasma proteins to the extent of 35 to 40%. Zidovudine is rapidly metabolized in the liver to the inactive 3 -azido-3 -deoxy-5 -0-beta-D-glucopyranuronosylthymi-dine (GAZT), which has an apparent elimination half-life of 1 hour. Zidovudine undergoes glomerular filtration and active tubular secretion. Coadministration of zidovudine with agents such as dapsone, pentamidine, amphotericin B, flucytosine, vincristine, vinblastine, adriamycin, and interferon with potential to cause nephrotoxicity or cytotoxicity to hematopoietic elements, enhance its risk of adverse effects. Probenecid will inhibit the renal excretion of zidovudine. 

Ferrero ME, Ferrero E, Gaja G, Bemelli-Zazzera A (1976) Adriamycin energy metabolism and mitochondrial oxidations in the heart of treated rabbits. Biochem Pharmacol... 

Seraydarian MW, Artaza L, Goodman MF (1977) Adriamycin effect on mammalian cardiac cells in culture. I. Cell population and energy metabolism. J Mol Cell Cardiol 9 375-382 Serrano J, Palmeira CM, Kuehl DW, Wallace KB (1999) Cardioselective and cumulative oxidation of mitochondrial DNA following subchronic doxorubicin administration. Biochim Biophys Acta 1411 201-205... 

In view of the extensive metabolism of adriamycin and daunomycin it is important to distinguish between parent drug and metabolites in studies of the disposition of these drugs. This was not the case in the early studies and so care has to... 

Rose, ed.), pp. 239-291. Academic Press, London 1979 Martin, J.-F. Polyene macrolide antibiotics. In Secondary Products of Metabolism (A. H. Rose, ed.), pp. 355-387. Academic Press, London 1979 Shaw, G. J., Milne, G. W. A., Minghetti, A. Propionate precursors in the biosynthesis of dauno-mycin and adriamycin a nuclear magnetic resonance study. Phytochemistry 18, 178-179 (1979)... 

Neither adriamycin nor daunomycin is absorbed orally [128] due to hydrolysis in the g.i,t. and so they must be administered by i.v. infusion. Both drugs undergo metabolism [129,130] and the predominant metabolites are adriamyci-nol (83) and daunorubicinol (84) respectively, in which the 13-keto group has been reduced. The enzyme responsible is a cytoplasmic aldo-ketoreductase which is found in all tissues, the kidney having the highest activity [131,132]. This is not the only metabolic transformation however, both the parent drug and its 13-dihydro-metabolite are metabolised by microsomal enzymes. Most of the... 

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