Teratogenic interactions of consecutively administered cortisone and cyclophosphamide
Dostál, M.
Folia Morphologica 33(2): 201-208
1985
ISSN/ISBN: 0015-5640 PMID: 4029831 Document Number: 263870
The teratogenic effect of consecutive combinations of cortisone and cyclophosphamide was studied in the experimental model of induced cleft palate in random-bred ICR (Velaz) mice. Single doses of cyclophosphamide and cortisone were administered between the 11th and 14th day of pregnancy (the vaginal plug = day 1) with an interval of 24 or 48 hours. The effect of ten different combinations was compared with the effect of a single dose of cyclophosphamide or cortisone and was evaluated from the aspect of teratogenic interactions. The interaction result was found to be determined by the sequence of administration, as well as by the time. With the sequence cortisone + cyclophosphamide, and additive type of interaction was found after the combination days 12 + 13 of pregnancy. With the sequence cyclophosphamide + cortisone, however, the interaction after the combination days 11 + 13 and 13 + 14 of pregnancy was additive, while the combinations days 12 + 13 and 12 + 14 of gestation led to potentiation of the effect of the single single doses. The results show that the consecutive administration of drugs can be followed by potentiation of their teratogenic effect; the results are also discussed with reference to the effect of the single and repeated administation of the same drug.