| ID | 65139 |
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| Author |
Aly, Nagwa S. M.
Division of International Infectious Disease Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Matsumori, Hiroaki
Division of International Infectious Disease Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Dinh, Thi Quyen
Division of International Infectious Disease Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Sato, Akira
Division of International Infectious Disease Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Miyoshi, Shin-Ichi
Department of Sanitary Microbiology, Faculty of 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
Cao, Duc Tuan
Department of Pharmaceutical Chemistry and Quality Control, Faculty of Pharmacy, Hai Phong University of Medicine and Pharmacy
Kim, Hye-Sook
Division of International Infectious Disease Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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| Abstract | We have previously reported 1,2,6,7-tetraoxaspiro [7.11]nonadecane (N-89) as a promising antimalarial compound. In this study, we evaluated the effect of transdermal therapy (tdt) of N-89 in combination (tdct) with other antimalarials as an application for children. We prepared ointment formulas containing N-89 plus another antimalarial drug, specifically, mefloquine, pyrimethamine, or chloroquine. In a 4-day suppressive test, the ED50 values for N-89 alone or combined with either mefloquine, pyrimethamine, or chloroquine were 18, 3, 0.1, and 3 mg/kg, respectively. Interaction assays revealed that N-89 combination therapy showed a synergistic effect with mefloquine and pyrimethamine, but chloroquine provoked an antagonistic effect. Antimalarial activity and cure effect were compared for single-drug application and combination therapy. Low doses of tdct N-89 (35 mg/kg) combined with mefloquine (4 mg/kg) or pyrimethamine (1 mg/kg) gave an antimalarial effect but not a cure effect. In contrast, with high doses of N-89 (60 mg/kg) combined with mefloquine (8 mg/kg) or pyrimethamine (1 mg/kg), parasites disappeared on day 4 of treatment, and mice were completely cured without any parasite recurrence. Our results indicated that transdermal N-89 with mefloquine and pyrimethamine provides a promising antimalarial form for application to children.
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| Keywords | transdermal N-89
mefloquine
pyrimethamine
antimalarials
combination
in vivo
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| Published Date | 2023-03-01
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| Publication Title |
Pathogens
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| Volume | volume12
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| Issue | issue3
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| Publisher | MDPI
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| Start Page | 398
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| ISSN | 2076-0817
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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 by the authors.
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| File Version | publisher
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| PubMed ID | |
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| Related Url | isVersionOf https://doi.org/10.3390/pathogens12030398
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| License | https://creativecommons.org/licenses/by/4.0/
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| Citation | Aly, N.S.M.; Matsumori, H.; Dinh, T.Q.; Sato, A.; Miyoshi, S.-I.; Chang, K.-S.; Yu, H.S.; Cao, D.T.; Kim, H.-S. Pioneer Use of Antimalarial Transdermal Combination Therapy in Rodent Malaria Model. Pathogens 2023, 12, 398. https://doi.org/ 10.3390/pathogens12030398
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