Toxicological evaluation of the new calcium antagonist VULM 993.
The tolerance of the new calcium antagonist VULM 993 was investigated in a series of toxicological studies. The following results were obtained: the maximum tolerated oral dose in acute toxicity was 10,000 mg/kg for mice and 6600 mg/kg for rats, for venous administration it was 26.1 mg/kg in mice and 32.2 mg/kg in rats. In subacute oral toxicity test in rats, VULM 993 showed no toxic effect up to 300 mg/kg/d. The drug was not teratogenic in rats (5, 50 or 250 mg/kg/d, p.o.). VULM 993 did not show any positive response in tests for genotoxicity in vitro. Transplacental study of VULM 993 in rabbits indicated active placental barrier function in the late stage of pregnancy. The toxicological profile of VULM 993 is characterised by a high tolerance in all relevant species of experimental animals, and no biologically significant mutagenic potential was recorded.
Múcková
M
M
Drug Research Institute, Modra, Slovakia. muckova@vulm.sk
Ujházy
E
E
Sadlonová
I
I
Faberová
V
V
Dubovický
M
M
Hózová
R
R
Lazová
J
J
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002460:Cell Line; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects; D013141:Spiro Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013723:Teratogens
D002121:Calcium Channel Blockers; D011725:Pyridines; D013141:Spiro Compounds; D013723:Teratogens; C405569:VULM 993