Disposition kinetics in the rat fetus

Disposition kinetics of drug from the fetus were studied by subcutaneous injection of indomethacin, salicylic acid, and diazepam into the fetuses of the rats. The mean residence time (MRT) for drugs increased with the day of gestation and the clearance decreased. The values of MRT were in the order indomethacin greater than salicylic acid greater than diazepam, and degrees of the developmental change of MRT were in the order indomethacin greater than salicylic acid greater than diazepam. The steady-state volume of distribution (Vss) for drugs showed little change, corresponding to no significant change in the tissue/plasma drug concentration ratio. The developmental profile of the rate of transplacental transference calculated from a one-compartment open model decreased with the day of gestation.