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薬理と治療
- Authors: Yuko Akasaka1, Akira Hatta1, Miwa Takei1, Toshitsugu Sato1, Jost Leuschner2, Hideo Inoue1
Abstract
Monoamminium Glycyrrhizinate (MGL) has been used for the clinical therapies ofchronic hepatitis as well as allergic diseases in Japan. To complement the information of toxicologyunder the ICH Guideline, MGL was tested for the carcinogenic potential in rats andmice. The animals were treated with 15, 45 or 135 mg/kg(rats), 10, 30 or 90 mg/kg(malemice), and 5, 15 or 45 mg/kg(female mice)by subcutaneous administration daily for 104weeks. The dose levels of the high−dose groups were switched in the range between 67.5and 225 mg/kg(rats), 90 and 180 mg/kg(male mice), and 45 and 90 mg/kg(female mice),to result in a sufficient degree of toxicity as required by the ICH guidelines. In rats, a doserelated systemic toxicity was noted above all in the high−dose group. Both male and femalemice experiments were terminated at test week 94 instead of 104 weeks in accordance withthe termination criteria in the guidelines. All other mortality rates of the mice in all dosegroups were within the range of the control group. All neoplastic lesions recorded in thesestudies are commonly encountered in corresponding animals of these strains and ages. Type,incidence, and severity of the lesions recorded were not increased in MGL−treated animalsas compared to the control animals. Toxicokinetic evaluation revealed a dose−dependent linearexposure to glycyrrhizin and glycyrrhetic acid. It is concluded that MGL given subcutaneouslydaily for 104 weeks has no carcinogenic potential in rats and mice.(Jpn Pharmacol Ther 2009;37:181−96)KEY WORDS Glycyrrhizin, Carcinogenicity study, Subcutaneous administration, Rat,Mouse
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