Experimental studies on the toxicity of harringtonine and homoharringtonine
Yongji, Z.; Hui, Y.; Xueying, L.; Yongxing, Z.; Wenjun, L.; Xueli, L.; Yuying, Y.
Chinese Medical Journal 92(3): 175-180
1979
ISSN/ISBN: 0366-6999 PMID: 109256 Document Number: 142297
Harringtonine (HA) and homoharringtonine (HO), 2 new antileukemic agents, are submitted to experimental toxicity studies in mice, rabbits and dogs. The organs involved in rabbits and dogs after 5 or 7 days' treatment with either alkaloid are chiefly the gastrointestinal tract, heart and hematopoietic organs. Most deaths are attributable to cardiac dysfunction. In only some of the animals receiving lethal doses moderate hepatic and renal damage occur. When 3 courses of treatment are given no other significant sign of toxicity is observed. The cardiac and hematopoietic toxicities appear to be moderately cumulative. All toxicities observed are dose-dependent and completely reversible upon discontinuation of treatment. No significant delayed toxicity is observed during the observation period of 6 wk or more. Neither inter- or intra-species difference nor sex-related difference in qualitative toxicity of HA or HO is observed. The established TDHS are 0.42 mg/kg of HA and 0.16 mg/kg day .times. 7 of HO for dogs. HO is much more potent than HA quantitatively; qualitatively they do not differ from each other.