ID | 67747 |
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Author |
Aly, Nagwa S. M.
Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Matsumori, Hiroaki
Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Dinh, Thi Quyen
Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Sato, Akira
Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Miyoshi, Shin-ichi
Department of Sanitary Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Chang, Kyung-Soo
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan
Yu, Hak Sun
Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University
Kubota, Takaaki
Department of Natural Products Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Kurosaki, Yuji
Department of Pharmaceutical Formulation Design, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kaken ID
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Cao, Duc Tuan
Department of Pharmaceutical Chemistry and Quality Control, Faculty of Pharmacy, Hai Phong University of Medicine and Pharmacy
Rashed, Gehan A.
Department of Parasitology, Benha Faculty of Medicine, Benha University
Kim, Hye-Sook
Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Abstract | Despite the recent progress in public health measures, malaria remains a troublesome disease that needs to be eradicated. It is essential to develop new antimalarial medications that are reliable and secure. This report evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo. After a single oral dose (75 mg/kg) of N-89, its pharmacokinetic parameters were measured, and t1/2 was 0.97 h, Tmax was 0.75 h, and bioavailability was 7.01%. A plasma concentration of 8.1 ng/ml of N-89 was maintained for 8 h but could not be detected at 10 h. The dose inhibiting 50% of parasite growth (ED50) and ED90 values of oral N-89 obtained following a 4-day suppressive test were 20 and 40 mg/kg, respectively. Based on the plasma concentration of N-89, we evaluated the antimalarial activity and cure effects of oral N-89 at a dose of 75 mg/kg 3 times daily for 3 consecutive days in mice harboring more than 0.5% parasitemia. In all the N-89- treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days. Additionally, administering oral N-89 at a low dose of 50 mg/kg was sufficient to cure mice from day 6 without parasite recurrence. This work was the first to investigate the pharmacokinetic characteristics and antimalarial activity of N-89 as an oral drug. In the future, the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated.
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Keywords | New antimalarial candidate
oral N-89
pharmacokinetics
in vivo
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Published Date | 2023-08-21
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Publication Title |
Parasites, Hosts and Diseases
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Volume | volume61
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Issue | issue3
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Publisher | Korean Society for Parasitology
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Start Page | 282
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End Page | 291
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ISSN | 2982-5164
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2023 The Korean Society for Parasitology and Tropical Medicine
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File Version | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
Related Url | isVersionOf https://doi.org/10.3347/phd.23044
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License | https://creativecommons.org/licenses/by-nc/4.0
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Funder Name |
Ministry of Education, Culture, Sports, Science and Technology
Japan Agency for Medical Research and Development
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助成番号 | JP22wm0125004
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