Drug development and industrial pharmacy
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Loperamide is a peripherally acting antidiarrheal opioid with some affinity for P-glycoprotein (P-gp). One of the main reasons for its lack of central nervous system (CNS) activity is a combination first-pass metabolism and P-gp-mediated efflux preventing brain penetration. It was assumed that P-gp would also have a similar effect at the intestinal tract, limiting loperamide systemic absorption. However, previous in vitro studies had not determined loperamide flux using pH gradients present in the intestinal tract. Hence, our aim was to determine the influence of pH gradient conditions on the gastrointestinal uptake of loperamide, including any changes to its P-gp-mediated efflux. ⋯ P-gp-mediated efflux of loperamide is supplemented under pH gradient conditions. Hence, drugs used to decrease acid secretion in the stomach could result in higher plasma loperamide levels based on our in vitro system reflecting the in vivo environment. The addition of a P-gp inhibitor could potentially further increase the gastrointestinal absorption of loperamide.