title: The effect of phenobarbital and dexamethasone on hepatic cytochrome P-450 and alpha 1-acid glycoprotein in maternal and fetal guinea pigs.
abstract: The effects of phenobarbital (PB) and dexamethasone (DX) on maternal and fetal hepatic cytochrome P450 content, benzphetamine (BzP) demethylation activity, the plasma concentration of alpha 1-acid glycoprotein (AGP), and the binding of propranolol (PPL) were examined in guinea pigs. In maternal guinea pigs, PB increased AGP-specific PPL binding by 131%, P450 by 94%, and BzP demethylation by 261%. DX only increased maternal AGP-specific PPL binding (122%). In fetal guinea pigs, neither PB nor DX resulted in significant increase for any of these parameters. The combination of PB and DX synergistically increased fetal P450 content (153% increase) and BzP demethylation (84% increase). In contrast, this combination treatment did not increase maternal P450 and BzP demethylation to a greater extent than by PB treatment alone nor did it increase the binding of PPL in PCA-treated fetal plasma. The synergy of P450 induction found in the fetus implicates glucocorticoids as important regulators of fetal hepatic microsomal enzyme maturation.
authors.affiliation: Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
authors.forename: M D
authors.initials: MD
authors.lastname: Hill
authors.forename: F P
authors.initials: FP
authors.lastname: Abramson
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003640:Dealkylation; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D007044:Hysterectomy; D008099:Liver / Q000201:enzymology*; D009961:Orosomucoid / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D011247:Pregnancy; D011433:Propranolol / Q000097:blood; D011485:Protein Binding / Q000187:drug effects
chemical_list: D001798:Blood Proteins; D009961:Orosomucoid; D001564:Benzo(a)pyrene; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D011433:Propranolol; D010634:Phenobarbital