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NF-E2-related factor 2 (Nrf2) is a transcriptional regulator of biological defense proteins, such as antioxidant proteins and phase II detoxification enzymes. Cytochrome P450 (P45 enzymes have been shown to regulate phase I metabolism of various drugs and are partially regulated by Nrf2; however, the influence of Nrf2 on drug pharmacokinetics is not known. Here, we showed that Nrf2 depletion prolonged the effect of pentobarbital, a sleep-promoting drug. Pretreatment with phenobarbital, a P450 inducer, shortens the sleeping time associa

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