Toxicokinetiek en embryotoxische effecten van Vitamine A na eenmalige orale toediening van verschillende doses retinylpalmitaat aan drachtige ratten

An experiment has been described in which the relationship between the pharmacokinetics and embryotoxic effects after a single oral dose of vitamin A is investigated. Retinyl palmitate in olive oil was orally administered to pregnant rats on day 10 of gestation at three different dose levels. The pharmacokinetics was followed for 24 hours and on day 11 and day 21 of gestation the conceptus were examined for malformations. From the pharmacokinetic data it appears that in rats after oral administration of retinyl palmitate no linear relationship could be detected between the internal dose (AUC and Cmax) of retinol, retinyl palmitate and retinyl stearate and the dose administered. Only a positive correlation between retinyl oleate and the dose could be found. In this experiment, no concentrations higher than the detection limit of retinoic acid were detected in the plasma of the rats. The embryotoxic effects, such as delayed closure of the neural tube at gestation day 11, and facial dysmorphogenis as determined at day 21, however, were clearly correlated to the dose