Menogaril: a new anthracycline agent entering clinical trials
Autor: | James C. Cradock, Kenneth G. Nelson, John P. Christopher, Jacqueline Plowman, J. Patrick McGovren, Mercedes Lassus |
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Rok vydání: | 1984 |
Předmět: |
Anthracycline
Administration Oral Antineoplastic Agents Pharmacology chemistry.chemical_compound Cricetulus Dogs Cricetinae medicine Animals Humans Pharmacology (medical) Doxorubicin Antitumor activity Clinical Trials as Topic Cardiotoxicity business.industry Daunorubicin Menogaril Rats Inbred Strains Neoplasms Experimental Macaca mulatta Rats Clinical trial Oncology Mechanism of action chemistry Nogalamycin Injections Intravenous Rabbit model Rabbits medicine.symptom business Mutagens medicine.drug |
Zdroj: | Investigational New Drugs. 2:359-367 |
ISSN: | 1573-0646 0167-6997 |
DOI: | 10.1007/bf00171586 |
Popis: | Menogaril [menogarol, 7(R)-O-methylnogarol, 7-OMEN] is a new anthracycline agent which was chosen for clinical trials based on: broad spectrum activity against a panel of murine tumors, lower cardiotoxicity than doxorubicin in the chronic rabbit model, differences in biochemical effects from other anthracyclines suggesting a possible difference in mechanism of action, murine antitumor activity by oral as well as parenteral routes. Biochemical studies indicated that, in comparison to doxorubicin, menogaril is bound weakly to DNA, inhibits RNA synthesis less, and has different cell cycle phase-specific cytotoxicity. Pharmacology studies in the mouse and dog using HPLC analytical methodology have shown multiexponential clearance from plasma and metabolism of menogaril to a material which co-chromatographs with N-demethylmenogaril in addition to at least two other metabolites of unknown structure. Oral bioavailability studies in the mouse showed significant absorption of menogaril from the gastrointestinal tract followed by first-pass metabolism. In acute toxicity studies in the rat, the dog, and the monkey, dose-related myelosuppression and gastrointestinal toxicity predominated. Phase I clinical trails on menogaril are currently in progress on a variety of schedules. |
Databáze: | OpenAIRE |
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