Lenalidomide Toxicology Study
Lenalidomide has the potential acute toxicity. Besides, the minimum lethal dose for oral administration in rodents is >2000 mg/kg/day. In the 26-week repeat dosing test in rats, after oral administration at 75, 150, 300 mg/kg/day, all three dose groups of animals produced reversible, drug-related pyelone mineralization, and the female monkey is more obvious. No adverse reaction dose (NOAEL) of 300 mg/kg/day was observed, which exceeds 50 times as the human daily exposure. Monkeys were respectively given lenalidomide at an oral dose of 4, 6 mg/kg/day for 20 weeks, indicating animal death and significant toxicity(that is, significantly reduced body weight, decreased red blood cell, white blood cell and platelet counts, multiple organ bleeding, gastrointestinal inflammation, lymphoid and bone marrow atrophy.) The monkeys were respectively orally given lenalidomide at 1,2 mg/kg/day for 1 year, showing reversible changes in the composition of myeloid cells, a slight decrease in the granulocyte/erythrocyte ratio, and atrophy of the thymus. The decrease of the white blood cell can be seen with the dose of 1 mg/kg/day, and this dose is approximately equal to the daily human exposure.
For Lenalidomide Ames Test, Human Lymphocyte Chromosome Aberration Test, Mouse Lymphoma Cell Assays, Syrian Hamster Embryo Cell Transformation Assays, and Rat Micronucleus Test, the results were all negative.