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This routes biologics and peptides directly into the CNS, bypassing first-pass hepatic metabolism and avoiding the highly selective BBB entirely

Much of the subsequent work has instead concerned effects some distance from sleep, including opioid withdrawal models, stress and corticotropin responses, and antioxidant activity

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Patients with mild to moderate renal impairment generally do not require dose adjustment, but closer monitoring may be warranted, particularly for signs of gastrointestinal adverse effects that could lead to dehydration and worsening renal function