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ID 67747
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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 publons researchmap
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
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.
Keywords
New antimalarial candidate
oral N-89
pharmacokinetics
in vivo
Published Date
2023-08-21
Publication Title
Parasites, Hosts and Diseases
Volume
volume61
Issue
issue3
Publisher
Korean Society for Parasitology
Start Page
282
End Page
291
ISSN
2982-5164
Content Type
Journal Article
language
English
OAI-PMH Set
岡山大学
Copyright Holders
© 2023 The Korean Society for Parasitology and Tropical Medicine
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DOI
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isVersionOf https://doi.org/10.3347/phd.23044
License
https://creativecommons.org/licenses/by-nc/4.0
Funder Name
Ministry of Education, Culture, Sports, Science and Technology
Japan Agency for Medical Research and Development
助成番号
JP22wm0125004