ININFA   02677
INSTITUTO DE INVESTIGACIONES FARMACOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Interaction between the efflux transporter BCRP ( ABCG2) and the anti-HIV drug efavirenz in rats
Autor/es:
PERONI RN, DI GENNARO SS, HÖCHT C., CHIAPPETTA DA.,SOSNIK A., RUBIO MC., BRAMUGLIA GF
Lugar:
Rosario - Argentina
Reunión:
Congreso; XLI Congreso Anual de la Asociación Argentina de Farmacología Experimental; 2009
Institución organizadora:
SAFE
Resumen:
    B4-86 INTERACTION         BETWEEN         THE            EFFLUX TRANSPORTER BCRP (ABCG2) AND THE ANTI-HIV DRUG EFAVIRENZ IN RATS. Peroni RNU, Di Gennaro SS1, Hocht C2, Chiappetta DA3, Sosnik A3, Rubio MCU, Bramuglia GF2. ´iNINFA (CONICET-UBA); 2Farmacologia (FFyB-UBA); 3Farmacotecnia (FFyB-UBA). Breast cancer resistant protein (BCRP/ABCG2) is an efflux transporter expressed in organs that influence the absorption and distribution of drugs, as the small intestine and the blood-brain barrier (BBB). The non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) is an anti-HIV drug that inhibits BCRP in vitro (Weiss et al, 2007) and chronic treatment with EFV increases BCRP expression in small intestine and BBB in rats (Peroni et al., 2008). This study was conducted to investigate the role of BCRP in the intestinal absorption and in the delivery to the central nervous system (CNS) of EFV and the influence of the chronic treatment with EFV on the expression of BCRP in adult male rats. Adult male Sprague-Dawley rats were used to perform all the experiments. The intestinal permeation rate was investigated in ileum everted sacs and the delivery to CNS of EFV was studied by microdialysis into the CNS. EFV was measured by HPLC-UV. In control rats, the concentration-dependent efflux of EFV (1-10 mM) observed in ileum everted sacs was almost completely block by pretreatment with the specific BCRP inhibitor fumitremorgin C (10 uM). Moreover, the delivery of EVF to CNS after a single i.v. administration of (20 mg/kg solved in Pluronic F127 10%, pH 5) was two-fold increased in rats pretreated with the BCRP inhibitor gefrtinib (20 mg/kg, i.p.). The intestinal absorption and the distribution into the CNS of EFV were modulated by BCRP in rats. Since, EFV itself could modulate BCRP expression could, in turn, influence the bioavailability and the delivery of this drug to target or sanctuary HIV-sites.