Circadian rhythm of embryotoxicity induced by sodium valproate in mice.

The influence of dosing time on embryotoxicity of valproate was investigated in ICR (Institute of Cancer Research, USA) mice under light-dark (12:12) cycle. A significant circadian rhythm was shown for embryotoxicity, with the highest value at 17:00 and the lowest at 01:00. No significant difference between injection at 17:00 and 01:00 was demonstrated for valproate concentrations in the embryo. The rhythm in the embryotoxicity seems to be related to the rhythm in the sensitivity to the drug. Embryotoxicity and valproate concentrations were significantly higher on gestational day 13 than day 7. The timing of drug administration (i.e., gestational stage and circadian phase) appears to be essential in the study of embryotoxicity of valproate in mice.