Effects of dienogest (a synthetic steroid) on coagulation, fibrinolysis, and platelet aggregation in female monkeys.
We investigated the effects of dienogest (0.1-10 mg/kg per day, p.o.) on coagulation, fibrinolysis and platelet aggregation in female rhesus monkeys. Then, we also examined those of medroxyprogesterone acetate (MPA, 10 mg/kg per day, p.o.) or danazol (10-1000 mg/kg per day, p.o.) on these parameters in the same species. In addition, we assessed the effects of dienogest (1 and 3 mg/kg per day, p.o.) or MPA (10 mg/kg per day, p.o.) on platelet aggregation and platelet lipids in female cynomolgus monkeys. At doses of 0.3 mg/kg or greater, dienogest increased the levels of several coagulation and anticoagulation factors, but had no effect on the prothrombin time, activated partial thromboplastin time, fibrinolysis, or platelet aggregation. MPA (10 mg/kg) had no effect on coagulation or fibrinolysis, but significantly potentiated platelet aggregation in response to ADP and collagen and also increased the platelet cholesterol-to-phospholipid ratio. Danazol (10 mg/kg or more) increased the activities of coagulation factors V, VII, VIII, X, XI, and XII in comparison to dienogest and MPA. Consequently, dienogest caused less potentiation of platelet aggregation than MPA and less potentiation of coagulation than danazol.
Toxicology Laboratory, Mochida Pharmaceutical Co., Ltd., Fujieda, Shizuoka, Japan. ykatsuki@mochida.co.jp
Y
Y
Katsuki
H
H
Nobukata
T
T
Ishikawa
Y
Y
Hamada
M
M
Sato
Y
Y
Shibutani
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003613:Danazol / Q000494:pharmacology; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010743:Phospholipids / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*
D006727:Hormone Antagonists; D010743:Phospholipids; C023635:dienogest; D009277:Nandrolone; D002784:Cholesterol; D017258:Medroxyprogesterone Acetate; D003613:Danazol