PT  - JOURNAL ARTICLE
AU  - Yun-Chen Tien
AU  - Stephanie C Piekos
AU  - Chad Pope
AU  - Xiao-bo Zhong
TI  - Phenobarbital Treatment at a Neonatal Age Results in Decreased Efficacy of Omeprazole in Adult Mice
AID  - 10.1124/dmd.116.073601
DP  - 2017 Jan 01
TA  - Drug Metabolism and Disposition
PG  - dmd.116.073601
4099  - http://dmd.aspetjournals.org/content/early/2017/01/06/dmd.116.073601.short
4100  - http://dmd.aspetjournals.org/content/early/2017/01/06/dmd.116.073601.full
AB  - 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 co-administrated, 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 is to investigate the consequence of neonatal drug exposure on efficacy of other drugs administered to 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 receive single or multiple doses of phenobarbital at a neonatal age. This effect is due to the persistent induction of cytochrome P450 enzymes after neonatal phenobarbital treatment. Our data indicates that DDIs may result from drugs administered in the past in an animal model and should prompt reevaluation of how drug interactions are viewed and avoided in today’s clinical practice to establish a precision medicine model in future.