CIRCADIAN-RHYTHM OF EMBRYOTOXICITY INDUCED BY SODIUM VALPROATE IN MICE

The influence of dosing time on embryotoxicity of valproate was invest igated in ICR (Institute of Cancer Research, USA) mice under light-dar k (12:12) cycle. A significant circadian rhythm was shown for embryoto xicity, with the highest value at 17:00 and the lowest at 01:00. No si gnificant difference between injection at 17:00 and 01:00 was demonstr ated for valproate concentrations in the embryo. The rhythm in the emb ryotoxicity seems to be related to the rhythm in the sensitivity to th e drug. Embryotoxicity and valproate concentrations were significantly higher on gestational day 13 than day 7. The timing of drug administr ation (i.e., gestational stage and circadian phase) appears to be esse ntial in the study of embryotoxicity of valproate in mice.