Perfil farmacocinético de nanopartículas de poli (metil metacrilato) contendo Praziquantel

Content Provider	Semantic Scholar
Author	Malhado, Mayara
Copyright Year	2015
Abstract	Praziquantel (PZQ) is the drug recommended by the World Health Organization for the treatment of schistosomiasis. In Brazil it is comercialised only in tablet, which complicates the treatment of children because of the difficulty of adapting the dose , and its extremely bitter taste. In this way, PZQ loaded in Poly(methyl methacrylate) Nanoparticle (PMMA-NP) were developed at Laboratório de Engenharia de Polimerização (COPPE –UFRJ), in order to develop PZQ suspension. This study aimed to evaluate the pharmacokinetic profile of PZQ loaded in nanoparticles ( PZQ -NP ) and compare it to the pharmacokinetic profile of PZQ administered in free form ( PZQ -L ) , as preclinical phase of the new pharmaceutical formulation development. Wistar rats, femeles, weighing nearby 300 g were used, was the experimental model employed. Blood was collected at 0, 5 min, 10 min , 15 min, 20 min, 30 min , 1 h 1:30 h , 2 h , 4 h, 8 h , 10 h , 12 h and 24 h after orally administration at a single dose of 60 mg / kg PZQ suspended in 1 ml of water containing 2% Cremophor® ( NP PZQ groups and PZQ L) or 1 ml of vehicle (control group). The handling and procedures with animals were approved by the Ethics Committee on Animal Use of Universidade Federal Fluminense. PZQ was extracted from plasma by liquid-liquid extraction with terc-butyl methyl ether. Diazepam was used as internal standard and the analysis of samples was performed by High Performance Liquid Chromatography Efficiency tandem Mass Spectrometry. The values obtained for Maximum Concentration (Cmax) and Area Under Curve (ASC0-t and ASC0 0-∞ ) for group PZQ-NP were about 3 times lower compared to PZQ-L group . However , the time for achieving maximum concentration ( Tmax ), the elimination constant (Ke) and the half-life time of elimination (T 1/2β) were not statistically different. These results suggest that the absorption is probably the rate-limiting step for obtaining better pharmacokinetic parameters of PZQ administrated on PMMA nanoparticles. Thus, further studies are needed to understand both the PMMA – PZQ absorption mechanisms, as the process of drug release through polymer matrix in vivo, in order to enhanced the nanosystem and then the product to become available for clinical use. Palavras chaves: Praziquantel, Poly (methyl methacrilate) Nanoparticle, pharmacokinetic.
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Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article