Summary of safety tests of ethyl apovincaminate.

Subchronic toxicity test (4-week p.o. on rats with 25 and 100 mg/kg; 3-month i.p. with 5 and 25 mg/kg; 3-month i.v. with 2 and 5 mg/kg daily doses on dogs) and chronic toxicity tests (6-month p.o. on rats with 25, 50 and 100 mg/kg and on dogs with 5 and 25 mg/kg daily doses) were performed with ethyl apovincaminate (RGH-4405, Cavinton), a cerebral vasodilatory compound, to study adverse effects in adult age. Reproduction tests (male and female fertility test on rats p.o. with 10 and 50 mg/kg; teratogenicity test in midpregnancy on rats p.o. with 12.5, 25, 50 mg/kg, 15, 50, 150 mg/kg, and 15, 45, 135 mg/kg daily doses, i.v. with 3.13, 6.25 and 12.5 mg/kg daily doses; on rabbits p.o. with 6, 12 and 18 mg/kg daily doses; peri- and postnatal studies in late pregnancy on rats p.o. with 15, 45 and 135 mg/kg i.v. with 4.13, 6.25, and 12.5 mg/kg daily doses) were carried out to study harmful effects in various early phases of life. Local tolerance was studied after i.m. and i.v. application. It was concluded that the planned 3 X 5 or 3 X 10 mg daily oral dose, 1 X 10 mg i.v. dose of Cavinton were safe for human application in adult age. Although the compound proved not to be teratogenic, it is not recommended for administration to pregnant women because of liability of increased sensitivity in pregnancy. Therapy of women in fertile age should be interrupted in case of pregnancy.