Pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics: Niclosamide as a case study
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224002786 |
| _version_ | 1797248408150343680 |
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| author | Jeong In Seo Geun-woo Jin Hye Hyun Yoo |
| author_facet | Jeong In Seo Geun-woo Jin Hye Hyun Yoo |
| author_sort | Jeong In Seo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T20:14:07Z |
| format | Article |
| id | doaj.art-5023f4f258ce4f4ea6397e43e8c783d4 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-24T20:14:07Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-5023f4f258ce4f4ea6397e43e8c783d42024-03-23T06:22:59ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-04-01173116394Pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics: Niclosamide as a case studyJeong In Seo0Geun-woo Jin1Hye Hyun Yoo2Pharmacomicrobiomics Research Center and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-Do, South KoreaR&D Center CnPharm Co. LTD, Seoul 03759, South KoreaPharmacomicrobiomics Research Center and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-Do, South Korea; Correspondence to: Pharmacomicrobiomics Research Center and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do 15588, South Korea.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.http://www.sciencedirect.com/science/article/pii/S0753332224002786Drug repurposingNiclosamideAbsorptionMetabolismDrug-drug interactions |
| spellingShingle | Jeong In Seo Geun-woo Jin Hye Hyun Yoo Pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics: Niclosamide as a case study Biomedicine & Pharmacotherapy Drug repurposing Niclosamide Absorption Metabolism Drug-drug interactions |
| title | Pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics: Niclosamide as a case study |
| title_full | Pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics: Niclosamide as a case study |
| title_fullStr | Pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics: Niclosamide as a case study |
| title_full_unstemmed | Pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics: Niclosamide as a case study |
| title_short | Pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics: Niclosamide as a case study |
| title_sort | pharmacokinetic considerations for enhancing drug repurposing opportunities of anthelmintics niclosamide as a case study |
| topic | Drug repurposing Niclosamide Absorption Metabolism Drug-drug interactions |
| url | http://www.sciencedirect.com/science/article/pii/S0753332224002786 |
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