Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-Trifluoroacetyladriamycin-14-valerate (AD-32) is superior to Adriamycin in murine L1210 and P388 leukemias and in a number of solid tumor systems, including Ridgway osteogenic sarcoma and Lewis lung carcinoma. In preclinical toxicology studies, AD-32 was less toxic than Adriamycin in both tumor- and non-tumor-being mice and in rabbits. An initial clinical trial was carried out in 23 patients who received a total of 74 courses of AD-32 over a dose range of 100--700 mg/m2 administered at 21-day intervals. Hydrocortisone given during the period of infusion prevented all clinical manifestations of acute toxicity. The AD-32 dose-limiting toxicity, leukopenia, was comparable to that of Adriamycin at a dose of 10:1, but at these equivalently myelosuppressive doses, AD-32 induced less gastrointestinal toxicity and alopecia than Adriamycin and it did not cause local tissue damage following inadvertent paravenous extravasation. Although two responses are reported, the therapeutic activity of AD-32 cannot be assessed because of an inadequate number of patients in any given tumor type. A phase II study is being initiated at a dose of 600 mg/m2 given at 21-day intervals.
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PMID:Initial clinical evaluation of N-trifluoroacetyladriamycin-14-valerate (AD-32), an adriamycin analog. 45 34

A thin-layer chromatographic method has been developed for the detection and measurement of N-trifluoroacetyladriamycin-14-valerate (AD 32) and its major metabolite trifluoroacetyladriamycin (AD 41). The procedure gives satisfactory linearity over a large range of concentrations. The coefficient of variability is about 10% over the entire range of usable concentrations, giving good reproducibility; sensitivity is 25 ng for both AD 32 and AD 41. Analysis is specific for AD 32 and AD 41 since adriamycin or more polar metabolites can be differentiated. Recovery is high (85-90%) and the method is simple and economical to use. Pharmacokinetics of AD 32 and AD 41 are reported in blood and some tissues of mice bearing Lewis Lung carcinoma.
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PMID:Quantitative thin-layer chromatographic measurement of n-trifluoroacetyladriamycin-14-valerate (AD 32) and trifluoroacetyladriamycin (AD 41) in blood and tissues. 54 71

A comparative investigation of the antineoplastic activity of adriamycin and its derivative, N-trifluoroacetyladriamycin-14-valerate (AD 32), was conducted in murine tumor models employing different treatment schedules and injection routes. In all conditions tested, ie, ascitic and disseminated L1210 leukemia, ascitic LSTRA lymphoma, and advanced Lewis lung carcinoma, AD 32 was significantly more effective in terms of lifespan prolongation and induction of cures than optimal adriamycin treatments. As with adriamycin, AD 32 was ineffective on ic transplanted L1210 leukemia.
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PMID:Comparative antineoplastic activity of adriamycin and N-trifluoroacetyladriamycin-14-valerate. 62 89

N-Trifluoroacetyladriamycin-14-valerate (AD 32) is an analog of doxorubicin whose chemico-physical characteristics are nontypical compared to the parent compound. Its most interesting feature is the lack of capacity to intercalate with DNA; thus, its mechanism of action as an antitumoral drug is still unknown. The N-trifluoroacetyl bond on the glycoside moiety is very stable and does not easily undergo enzymatic hydrolysis. Conversely, the valerate ester is split very rapidly by tissue and blood hydrolases. In this paper we present a kinetic study on AD 32, and we additionally follow the formation and disappearance of its metabolite, N-trifluoroacetyladriamycin (AD 41). Peak levels, areas under the curve, and beta-half-lives of AD 32 and AD 41 after an iv injection of 80 mg/kg of AD 32 to Lewis lung carcinoma-bearing mice are presented. The results indicated very rapid disappearance of AD 32 from blood and tissues, whereas AD 42 persisted for much longer. Moreover, all of the tissues taken into consideration were able to hydrolyze AD 32 to AD 41, suggesting that this compound plays an important role in the antitumoral activity of AD 32.
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PMID:Possible relevance of N-trifluoroacetyladriamycin (AD 41) in the antitumoral activity of N-trifluoroacetyladriamycin-14-valerate (AD 32) in tumor-bearing mice. I. Pharmacokinetic evidence. 744 25