Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation
In vivo analysis of the safety of high dose ivermectin with a Corydoras fish animal model.
Madrid et al., 31 Dec 2020, peer-reviewed, 8 authors.
Abstract: Heliyon 7 (2021) e05820
Contents lists available at ScienceDirect
Heliyon
journal homepage: www.cell.com/heliyon
Research article
Safety of oral administration of high doses of ivermectin by means of
biocompatible polyelectrolytes formulation
Rafael R.M. Madrid a, Patrick D. Mathews a, *, Ana C.M.F. Patta a, Anai P. Gonzales-Flores b, c,
Carlos A.B. Ramirez a, Vera L.S. Rigoni a, Marcos Tavares-Dias d, Omar Mertins a, **
a
Laboratory of Nano Bio Materials (LNBM), Department of Biophysics, Paulista Medical School, Federal University of Sao Paulo (UNIFESP), 04023-062 Sao Paulo, SP,
Brazil
b
Post-Graduate Program in Tropical Biodiversity, Federal University of Amap
a, 68903-419 Macap
a, AP, Brazil
c
Institute of Research of the Peruvian Amazon (IIAP, AQUAREC), 17000 Puerto Maldonado, Peru
d
Embrapa Amapá , 68903-419 Macap
a, AP, Brazil
A R T I C L E I N F O
A B S T R A C T
Keywords:
High dosage
Drug repurposing
Animal model
Histochemistry
Formulation
Immunofluorescence
The FDA-approved drug ivermectin is applied for treatments of onchocerciasis and lymphatic filariasis. The anticancer and anti-viral activities have been demonstrated stressing possibilities for the drug repurposing and
therefore new information on high dosage safety is on demand. We analyzed in vivo tissue responses for high doses
of ivermectin using Corydoras fish as animal model. We made intestinal histology and hematologic assays after
oral administration of ivermectin transported with polyelectrolytes formulation. Histology showed any apparent
damage of intestinal tissues at 0.22–170 mg of ivermectin/kg body weight. Immunofluorescence evidenced
delocalization of Myosin-Vb at enterocytes only for the higher dose. Hematology parameters showed random
variations after 7 days from administration, but a later apparent recover after 14 and 21 days. The study evaluated
the potential of high doses of oral administration of ivermectin formulation, which could be an alternative with
benefits in high compliance therapies.
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