MOLECULAR DOCKING-BASED CLASSIFICATION OF P-GLYCOPROTEIN INHIBITORS AND THEIR POTENTIAL INTERACTION WITH DIGOXIN
AbstractP-glycoprotein (P-gp) is a membrane efflux transporter influencing drug absorption and disposition. Inhibiting P-gp may increase plasma levels of substrates like digoxin, heightening toxicity risk. This study aimed to classify 35 drugs based on their molecular docking-derived binding affinity to P-gp and their potential to inhibit digoxin transport, using estimated inhibition constants (Ki). Docking simulations were performed using AutoDockVina. Physicochemical parameters were gathered, and binding energies (ΔG) were converted to Ki values. Drugs were ranked using a Ki ratio relative to digoxin (Ki-drug/Ki-dgx). Four drugs (conivaptan, telmisartan, indinavir, and troglitazone) showed stronger affinity than digoxin (Ki < Ki-dgx), indicating high risk of interaction. Diltiazem displayed indirect interaction through aldosterone modulation. The classification revealed 12% strong, 56% moderate, and 32% weak inhibitors. This computational framework allows early screening of P-gp-mediated drug–drug interactions and can guide clinical decisions involving digoxin therapy in polypharmacy settings.
Article Information
36
3488-3491
512 KB
3
English
IJPSR
R. Lozano * and C. Bona
Department of Pharmacy, University Clinical Hospital “Lozano Blesa”, Zaragoza, Spain. C/San Juan Bosco, 15 50009 Zaragoza, Spain.
jrlozanoo@gmail.com
01 July 2025
19 July 2025
22 July 2025
10.13040/IJPSR.0975-8232.16(12).3488-91
01 December 2025
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