Pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics: Niclosamide as a case study - 22/03/24
Abstract |
Recently, anthelmintics have showcased versatile therapeutic potential in addressing various diseases, positioning them as promising candidates for drug repurposing. However, challenges such as low bioavailability and a lack of a solid pharmacokinetic basis impede successful repurposing. To overcome these flaws, we aimed to investigate the key pharmacokinetic factors of anthelmintics mainly focusing on the absorption, distribution, and metabolism profiles by employing niclosamide (NIC) as a model drug. The intestinal permeability of NIC is significantly influenced by solubility and doesn't function as a substrate for efflux transporters. It showed high plasma protein binding. Also, the metabolism study indicated that NIC would have low metabolic stability by extensively undergoing the intestinal glucuronidation. Additionally, we investigated the CYP-mediated drug-drug interaction potential of NIC in both direct and time-dependent ways. NIC showed strong inhibitory effects on CYP1A2 and CYP2C8 and is not likely to become a time-dependent inhibitor. Our findings could contribute to the identification of essential factors in the pharmacokinetics of anthelmintics, potentially facilitating their repositioning.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Anthelmintics have gained significant attention as promising candidates for drug repurposing. |
• | Low bioavailability and a lack of pharmacokinetic basis hinder their successful repositioning. |
• | NIC serves as a model drug to explore key pharmacokinetic attributes that influence anthelmintic’s repurposing potential. |
• | Our study provides a demonstration of NIC's absorption, distribution, metabolism, and CYP-mediated DDI potential. |
Keywords : Drug repurposing, Niclosamide, Absorption, Metabolism, Drug-drug interactions
Plan
Vol 173
Article 116394- avril 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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