title: Phenobarbital Treatment at a Neonatal Age Results in Decreased Efficacy of Omeprazole in Adult Mice.
abstract: Drug-drug interactions (DDIs) occur when the action of one drug interferes with or alters the activity of another drug taken concomitantly. This can lead to decreased drug efficacy or increased toxicity. Because of DDIs, physicians in the clinical practice attempt to avoid potential interactions when multiple drugs are coadministrated; however, there is still a large knowledge gap in understanding how drugs taken in the past can contribute to DDIs in the future. The goal of this study was to investigate the consequence of neonatal drug exposure on efficacy of other drugs administered up through adult life. We selected a mouse model to test phenobarbital exposure at a neonatal age and its impact on efficacy of omeprazole in adult life. The results of our experiment show an observed decrease in omeprazole's ability to raise gastric pH in adult mice that received single or multiple doses of phenobarbital at a neonatal age. This effect may be associated with the permanent induction of cytochrome P450 enzymes in adult liver after neonatal phenobarbital treatment. Our data indicates that DDIs may result from drugs administered in the past in an animal model and should prompt re-evaluation of how DDIs are viewed and how to avoid long-term DDIs in clinical practice.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut.
authors.forename: Yun-Chen
authors.initials: YC
authors.lastname: Tien
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Piekos
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut.
authors.forename: Chad
authors.initials: C
authors.lastname: Pope
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut xiaobo.zhong@uconn.edu.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Zhong
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D065693:Cytochrome P-450 Enzyme Inducers / Q000008:administration & dosage* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D005744:Gastric Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008810:Mice, Inbred C57BL; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D010634:Phenobarbital / Q000008:administration & dosage* / Q000378:metabolism; D013270:Stomach / Q000187:drug effects*
chemical_list: D065693:Cytochrome P-450 Enzyme Inducers; D003577:Cytochrome P-450 Enzyme System; D009853:Omeprazole; D010634:Phenobarbital