Estudo pré-clinico da farmacocinética do praziquantel em formas micro e nanoestruturadas utilizando ratos Wistar

Abstract

Schistosomiasis is a tropical parasitic disease caused by Schistosoma, with treatment and prophylaxis relying exclusively on praziquantel (PZQ). However, PZQ's limited water solubility compromises its bioavailability, a critical factor for its therapeutic efficacy. Available in Brazil as 600 mg racemic tablets, the drug contains a mixture of levo-PZQ (L-PZQ), responsible for pharmacological activity, and dextro-PZQ (D-PZQ), which contributes to the bitter taste and adverse effects. The absence of suitable formulations for the pediatric population necessitates tablet splitting, resulting in inaccurate dosing and exacerbated side effects due to the unpleasant taste. To address these challenges, a new active ingredient based on L-PZQ micro and nanocrystals was developed, aiming to improve both bioavailability and drug acceptability. The present study aimed to evaluate the preclinical pharmacokinetics of these new formulations in Wistar rats following oral administration of a 60 mg/kg dose. Blood samples were collected via carotid artery cannulation and analyzed by HPLC-UV Vis for plasma PZQ quantification. Non-compartmental pharmacokinetic analysis revealed the following area under the curve (AU0-t) values: racemic PZQ, 1.63 ± 0.24 ug*h/mL; L-PZQ, 2.45 ± 0.52 ug*h/mL; L-PZQ microcrystals, 3.17 ± 1.08 ug*h/mL; and L-PZQ nanocrystals, 4.04 ± 1.04 ug*h/mL. Microcrystals oral relative bioavailability was about 130%, while nanocrystals showed about 165%. These results demonstrate a significant improvement in bioavailability for the new formulations, especially for the nanocrystals, providing crucial data for the development of future PZQ pharmaceutical formulations with potential to enhance therapeutic efficacy and pediatric acceptance. [resumo fornecido pelo autor]