ArticleCPT: pharmacometrics & systems pharmacology2026
Managing Drug-Drug Interactions Involving the Non-Prescription Opioid Loperamide Through Physiologically Based Pharmacokinetic Modeling.
Article in CPT: pharmacometrics & systems pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Loperamide is a widely used nonprescription peripherally acting opioid indicated for diarrhea. Loperamide undergoes extensive first-pass metabolism, primarily by cytochrome (CYP) 3A and CYP2C8, with minor contributions from CYP2B6 and CYP2D6, and intestinal efflux by P-glycoprotein (P-gp). Increasing case reports have described exaggerated peripheral opioid effects and cardiac toxicities when ultra-high doses (> 70 mg) of loperamide are consumed alone and with CYP or P-gp inhibitors. A physiologically based pharmacokinetic (PBPK) model for loperamide was developed, verified, and applied by simulating interactions with select inhibitor drugs. The model successfully described the pharmacokinetics of loperamide (4, 8, 16 mg loperamide•HCl) in healthy adults. The predicted area under the plasma concentration-time curve (AUC) and maximum concentration (C
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