Preclinical evaluation of the oral bioavailability of the anti-HIV agent efavirenz encapsulated in polymeric micelles: an in vitro-in vivo correlation study

CHIAPPETTA D.A.; HOCHT C.; TAIRA C.; SOSNIK A.

Porto Alegre

Congreso; 1er Congreso Sudamericano de Biofarmacia y Farmacocinética; 2010

Federacion Farmaceutica Sudamericana (FEFAS)

Introduction: Efavirenz (EFV) is a first-line antiretroviral used in the treatment of pediatric HIV/AIDS. EFV aqueous solubility is very low (4 ug/mL), and its bioavailability is 40-45%. Currently, there is a triglyceride liquid formulation of EFV that enables a more convenient dose adjustment and swallowing, though it is not available worldwide. More importantly, the oral bioavailability of EFV in this formulation is lower than that of the solid form. Our research group dedicates efforts to study cost-effective nanotechnological strategies to improve the pharmacotherapy of the pediatric HIV. In this context, we present the encapsulation of EFV in polymeric micelles of linear and branched poly(ethylene oxide)-poly(propylene oxide) block copolymers and their evaluation in vivo after oral administration [1]. Objectives: To encapsulate EFV in poly(ethylene oxide)-poly(propylene oxide) polymeric micelles. To assess the pharmacokinetics of the drug after oral administration in rats. To evaluate the correlation of the in vitro-in vivo data. Materials and methods: EFV was encapsulated in micelles of Pluronic® F127 10% at pH 5.0. The oral bioavailability the drug after oral administration of 20mg/ml solution (40 mg/kg and 80 mg/kg) was compared to that of an aqueous suspension and an oily solution of medium chain triglycerides in male Wistar rats (220-250 g). The concentration of EFV in plasma samples was analyzed by HPLC-UV. In vitro-in vivo correlation was determined using Microsoft® Excel 2003. Results: The administration of EFV in the aqueous micellar system allowed to obtain a significant increase in maximum plasma concentrations (Cmax) (40 mg/kg: 2.9 ± 0.7 mg/ml, 80 mg/kg: 7.1 ± 1.5 mg/ml, p