Induction of hepatic CYP2B in foetal and neonatal rats after maternal administration of phenobarbital

We examined hepatic cytochrome P450 (CYP) induction in rat foetuses and neo nates by phenobarbital administered through placenta or breast feeding. In an intraperitoneal study, phenobarbital was administered intraperitoneally to mother rats once a day for 7 consecutive days before delivery. The liver s were removed From foetuses, neonates, and mothers just before and 5 and 1 0 days after delivery. In oral administration study, water containing pheno barbital was given orally ad libitum from day 13 of pregnancy to 3 weeks af ter delivery (end of lactation). The livers were removed from neonates and mothers just before and one week after delactation. Phenobarbital administe red intraperitoneally increased both the activity and the protein expressio n of CYP2B in 5-day-old neonates, even though the administration ended befo re delivery. This increase had disappeared in 10-day-old neonates. In mothe r rats, phenobarbital increased CYP2B just before and 5 days after delivery , while no increase was detected 10 days after delivery Phenobarbital admin istered orally also increased both the activity and the protein expression of CYP2B of neonates and mothers during lactation and this increase also di sappeared 1 week after delactation. Neither activity nor protein expression of CYP3A were induced in perinates at any age examined in either administr ation route. In mother rats, increase in CYP3A was found only just before d elivery in the peritoneal administration study. Our results suggest that ph enobarbital administered through placenta or breast milk transiently induce s hepatic CYP2B in newborn rats but that the influence of phenobarbital doe s not last long.