| Abstrakt: |
Felodipine (4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylic acid 5-ethyl 3-methyl ester, CAS 72509-76-3), a vascular selective dihydropyridine calcium antagonist, was tested in three different reproduction studies in the rat. In fertility, teratology and peri-postnatal studies Sprague-Dawley rats were dosed by gavage with 10, 25 and 70 mumol/kg (fertility and teratology studies) or 3, 10 and 30 mumol/kg (peri-postnatal study). There were no increased incidences of external, visceral or skeletal malformations in the teratology study in groups treated with felodipine during organogenesis, compared with the control group. In the fertility and peri-postnatal studies, prolonged parturition and increased incidences of stillborn fetuses and postnatal death were observed in groups given 10 mumol/kg or more, but not at 3 mumol/kg. Similar to the findings in this study, nifedipine, nitrendipine, nicardipine, diltiazem and isradipine have all been reported to induce increased incidences of perinatal death in offsprings in peri-postnatal studies. Thus, the increased incidences of perinatal death (most likely secondary to inhibition of the uterine activity) seems to be a class effect common to all calcium antagonists. |
