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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
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.
Keywords
transdermal N-89
mefloquine
pyrimethamine
antimalarials
combination
in vivo
Published Date
2023-03-01
Publication Title
Pathogens
Volume
volume12
Issue
issue3
Publisher
MDPI
Start Page
398
ISSN
2076-0817
Content Type
Journal Article
language
English
OAI-PMH Set
岡山大学
Copyright Holders
© 2023 by the authors.
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isVersionOf https://doi.org/10.3390/pathogens12030398
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https://creativecommons.org/licenses/by/4.0/
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