Phenobarbital during pregnancy in mouse and man

Phenobarbital appears to produce similar behavioral effects on mice and humans with excitation at low and sedation or depression at higher doses. If plasma concentrations of phenobarbital reflect levels in other tissue, then brain concentrations producing excitation (near 10 micrograms/g) and depression (near 20 micrograms/g) are not substantially different for the two species. The doses needed to produce these levels are much higher in mice than man. Plasma concentrations of phenobarbital decline during pregnancy in humans. Whether this decline is accompanied by increased seizure frequency has not been confirmed empirically and whether pregnancy influences the frequency of seizures at all is controversial. The reduction in phenobarbital levels in plasma or serum during pregnancy has been confirmed in rodents. Two of these studies however reported no difference brain concentrations of the drug during pregnancy. One study indicated increased potency of the drug, however this was not confirmed by the other two reports. The effects of phenobarbital on the progression of pregnancy and on offspring is not well defined in humans partly because the disease and the treatment effects are confounded. There are a few studies however which suggest that the effects might be drug specific. Animal studies in this area differ substantially from humans in design making any comparison tentative. The effects of the drug on pregnancy and neonates in rodents depends on the method of administering the drug and dose. Drug administration via the diet can provide high blood levels in the dams and causes lowered birthweight as well as several anatomical and hormonal abnormalities in offspring. This procedure, however, also severely reduced food intake and weight gains during pregnancy which might confound drug effects with nutritional deficiency. The drug can be injected in doses which produce plasma levels well within the therapeutic range for humans. Under these conditions the drug is less detrimental to the progression of pregnancy, however, the higher doses can increase neonatal mortality and reduce body weight of surviving offspring. Although mortality and body weight are not adversely effected by lower doses, changes are still apparent in the behavior as well as several biochemical parameters. Fostering studies on animals suggest that the effects of maternal injections of phenobarbital on offspring are due to the IN UTERO exposure rather than postnatal maternal factors and that effects produced by fostering itself may be confounded with the drug effects.