RESUMO
On the 9th day of gestation of rabbits the embryotoxic effects of cyclophosphamide were tested in vivo by i.v. injection (20, 40 and 80 mg/kg) and by injection into the yolk sac of rabbit embryos (20 micrograms, 80 micrograms 320 micrograms/blastoderm; yolk-sac-method). Furthermore pharmacological studies were undertaken to investigate cyclophosphamide and its metabolism in the blastoderm (york sac fluid and embryo). When applied by i.v. injection, cyclophosphamide was embryolethal and teratogenic in a dose-dependent manner. No embryotoxic effects could be observed by injection of unchanged cyclophosphamide into the yolk sac of rabbit embryos. Pharmacokinetic studies did not show any metabolism in the blastoderm by injection or unchanged cyclophosphamide into the yolk sac. The embryotoxicity of unchanged cyclophosphamide is discussed.
