Author/Authors :
Peccinini, Rosângela Gonçalves Department of Natural Active Principles and Toxicology - School of Pharmaceutical Sciences - University of Estadual Paulista - Araraquara - Sao Paulo, Brazil , Alzate, Manuel Alejandro Henao Department of Natural Active Principles and Toxicology - School of Pharmaceutical Sciences - University of Estadual Paulista - Araraquara - Sao Paulo, Brazil , Filho, Marco Antonio Ferraz Nogueira Department of Natural Active Principles and Toxicology - School of Pharmaceutical Sciences - University of Estadual Paulista - Araraquara - Sao Paulo, Brazil , Franchin, Taisa Busaranho Department of Natural Active Principles and Toxicology - School of Pharmaceutical Sciences - University of Estadual Paulista - Araraquara - Sao Paulo, Brazil , Oliveira, Jonata Augusto de Department of Natural Active Principles and Toxicology - School of Pharmaceutical Sciences - University of Estadual Paulista - Araraquara - Sao Paulo, Brazil , Candido, Caroline Damico Department of Natural Active Principles and Toxicology - School of Pharmaceutical Sciences - University of Estadual Paulista - Araraquara - Sao Paulo, Brazil , Furini, Junior Department of Clinical Analysis - Toxicological and Bromatological - School of Pharmaceutical Sciences - University of Sao Paulo - Ribeirao Preto - Sao Paulo, Brazil , Albuquerque, Sergio de Department of Clinical Analysis - Toxicological and Bromatological - School of Pharmaceutical Sciences - University of Sao Paulo - Ribeirao Preto - Sao Paulo, Brazil
Abstract :
Benznidazole and nifurtimox are two drugs that are used to treat trypanosomiasis. Ursolic acid (UA)
reportedly acts against trypomastigotes and intracellular amastigotes of Trypanosoma cruzi.
Accordingly, it is expected to have therapeutic benefits in the treatment of trypanosomiasis.
Therapeutic application of a compound requires the investigation of its pharmacokinetic properties
in order to obtain relevant information to design the in vivo assays and dose regimen. Regarding this,
the current study aimed to evaluate the pharmacokinetic profile of UA administered to rats at
different doses and routes (i.e., 1 mg/kg intravenously and 20 and 50 mg/kg orally). According to the
results, the oral bioavailability was significantly different between the two groups that orally received
the UA doses of 20 mg/kg (2.8%) and 50 mg/kg (1.55 %). The result suggests the interference of the
poor aqueous solubility of UA on its absorption process. The pharmacokinetic parameters related to
the distribution and elimination were similar. Accordingly, it can be concluded that at this dose range,
there is no saturation in this process rendering a linear the kinetics. The pharmacokinetic properties
of UA were observed in this study indicated that the improvement of water solubility in this medicine
through pharmacotechnical resources would be a great utility for its oral bioavailability and
development of a product with the potential therapeutic application. The oral administration of this
new pharmaceutical formulation should be investigated in future studies.
Keywords :
Trypanosomiasis , Ursolic acid , Pharmacokinetics , High-performance liquid chromatography
