A method to inject the umbilical vein of the rat

A technique for injection into the umbilical vein was developed for pharmacokinetic analysis of the fetus, using rats on days 18 and 20 of gestation. The fetus was drawn out of the amniotic sac and incubated in lactated Ringer's solution; this technique showed no influence on the activity of serum enzymes or drug metabolizing enzymes or on the elimination rate for p-phenylbenzoic acid (PPBA). Elimination rate constants (Kel) obtained by using the present method were 6.49 h-1 (18th day) and 5.17 h-1 (20th day) for PPBA, and 1.24 h-1 (18th day) and 0.765 h-1 (20th day) for indomethacin. The experimental results show that the present method gives the actual elimination rate constant of the fetus and distinguishes metabolites in the fetus from those formed in the mother. Indomethacin was found not to be metabolized by the fetus.