Thirty-day rat toxicity study reveals reversible liver toxicity of mifepristone (RU486) and metapristone

Toxicology Mechanisms and Methods
Yingying XiaoLee Jia

Abstract

Mifepristone (RU486) is an oral first-line contraceptive used by hundreds of millions of women, and recently it was tested for anticancer activity in both genders worldwide. We are developing metapristone (the N-monodemethyl RU486) as a potential metastasis chemopreventive. The present acute and 30-d subacute toxicity study aimed at examining and compared in parallel the potential toxicity of the two drugs. The single-dose acute toxicity and 30-d subacute toxicity studies were conducted in mice and rats, respectively, by gavaging metapristone or mifepristone at various doses. Blood samples and organs were collected for blood chemistry, hematology and histology analyses. Oral mifepristone (3000 mg/kg) caused 30% and 40% death in female and male mice, respectively, within 15 h post-dosing. In comparison, the same dose of metapristone produced 30% acute death in males only. Thirty-day oral administration of the two drugs to rats (12.5, 50 and 200 mg/kg/day) caused reversible hepatotoxicity that only occurred at 200 mg/kg/day group, evidenced by the elevated liver enzyme activity and liver organ weight. The present study, for the first time, reveals reversible hepatotoxicity in rats caused by the 30-d consecutive administration at ...Continue Reading

References

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Citations

Oct 31, 2019·The Journal of Clinical Endocrinology and Metabolism·Benjamin SmallShannon Whirledge
Mar 31, 2021·Acta Pharmacologica Sinica·Xin-Peng YaoHui-Chang Bi
Mar 9, 2020·Clinics and Research in Hepatology and Gastroenterology·Lucy MeunierHillaire-Buys Dominique

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