Preclinical pharmacokinetics of benznidazole-loaded interpolyelectrolyte complex-based delivery systems

GARCÍA, MÓNICA CRISTINA; GUZMAN, MARÍA LAURA; HIMELFARB, MARTÍN A.; LITTERIO, NICOLÁS J.; OLIVERA, MARÍA EUGENIA; JIMENEZ-KAIRUZ, ALVARO

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2018 vol. 122 p. 281 - 281

0928-0987

enznidazole (BZ), first-line drug for Chagas treatment, is available as immediate-release tablets. High frequency of administration, long-term therapy, and side effects of BZ conspire against treatment adherence, and negatively impact in therapeutic success. We have developed BZ-loaded interpolyelectrolyte complexes (IPECs) composed of polymethacrylates (EE-EL-BZ) or polysaccharides (Ch-AA-BZ) for controlled BZ release. This work aimed to evaluate their preclinical pharmacokinetics compared to Abarax® (reference treatment) and to correlate them with the in vitro BZ release. A randomization schedule with a 3 × 2 cross-over design was used. Each healthy dog received a single oral dose of 100 mg of BZ from EE-EL-BZ, Ch-AA-BZ or Abarax®. BZ quantification was performed in plasma by a validated HPLC-UV method. Moreover, in silico simulations using the pharmacokinetic software PK Solutions 2.0? were calculated for the multiple-dose administration at two dose regimens: 100&