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The reduction in AUC after oral administration can result from numerous mechanisms including: pH or bacterial-mediated metabolism of the drug within the GI tract, incomplete drug absorption from the GI tract, metabolism within the GI epithelium (which contains CYP3A4), excretion back into the GI tract by P-glycoprotein in the GI epithelium, hepatic metabolism, or biliary excretion into the GI tract
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Similarly, an animal study on cocks demonstrated that Mn supplementation led to a decline in reproductive hormone levels ( in vitro studies have reported a wide range of Mn-induced pulmonary effects, including lung damage, inflammation, alveolar macrophage infiltration, and oxidative stress ( Additionally, excessive Mn has been linked to metabolic disorders, including type II diabetes, obesity, and cardiovascular disease, with oxidative stress proposed as a key contributing factor ( 6 Disease modulation of Mn transport and metabolism Mn transport and metabolism are dynamically regulated across diverse disease states
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