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Dr. Gehan Abd El Rahman Osman Rashed :: Publications:

Title:
Evaluating the activity of N-89 as an oral antimalarial drug
Authors: Nagwa S. M. Aly1,2 , Hiroaki Matsumori1, Thi Quyen Dinh1, Akira Sato1,3, Shin-ichi Miyoshi4, Kyung-Soo Chang5, Hak Sun Yu6, Takaaki Kubota7, Yuji Kurosaki8, Duc Tuan Cao9, Gehan A. Rashed2, Hye-Sook Kim1,*
Year: 2023
Keywords: New antimalarial candidate, oral N-89, pharmacokinetics, in vivo
Journal: Not Available
Volume: Not Available
Issue: Not Available
Pages: Not Available
Publisher: Not Available
Local/International: International
Paper Link: Not Available
Full paper Gehan Abd El Rahman Osman Rashed_paper 6.pdf
Supplementary materials Not Available
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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