Teratogenicity study in rats of commonly used calcium channel blockers

ABSTRACT

Background: Calcium channel blockers (CCBs) are popular medicines used to treat hypertension, tachyarrhythmias or angina during pregnancy. Lack of adequate safety data has however created an uncertainty in the use of CCBs in pregnancy. Nifedipine has been reportedly associated with a variety of embryotoxic and fetotoxic effects in animals. Therefore, this study was undertaken to establish whether or not the commonly used CCBs (nifedipine and amlodipine) would produce teratogenic effects in rats.Methods: Twenty pregnant rats were randomly assigned to each of the treatment and control groups. Nifedipine and amlodipine were used in three dose levels of 5, 10, 20 mg/kg and 0.5, 1, 2 mg/kg body weight respectively to test its teratogenic effects. The maximum dose of the test drugs used in our study was ten times the maximum recommended human dose. The drugs were administered to the pregnant rats using nasogastric tubes from day 6 through day 15 of pregnancy. The number of live births, stillbirths, litter sizes, crown-rump lengths, birth weights and gross abnormalities of the pups delivered were observed and recorded. Skeletal changes and soft tissue changes were also observed in the pups delivered to treated pregnant rats.Results: It was found that nifedipine and amlodipine did not produce any teratogenic effects in rats at doses 2.5 to 10 times the recommended human dose. None of the pups showed any gross morphological, skeletal or visceral defects.Conclusions: Nifedipine and amlodipine appear to be safe during pregnancy in therapeutic doses.