Modulation of the efflux transporter BCRP (ABCG2) activity by the anti-HIV drug EFAVIRENZ in rats.

PERONI RN; RUBIO MC; BRAMUGLIA GF

Tandil, Provincia de Bs As

Congreso; XXXX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2008

Sociedad Argentina de Farmacología Experimental

OBJECTIVES: The safety and effectiveness of highly active antiretroviral therapy (HAART) is challenged by viral resistance to antiretrovirals and the frequent occurrence of drug interactions which may limit the access of these drugs to the target sites. In particular, drug distribution and elimination may be modified by active efflux transporters such as BCRP. Previous studies demonstrated significant inhibition of BCRP by the nonnucleoside reverse transcriptase inhibitor efavirenz in vitro (Weiss et al., 2007). The aim of this study was therefore to investigate the influence of the chronic treatment with efavirenz on the expression of BCRP in adult male Sprague-Dawley rats. METHODS: BCRP expression was assessed by Western Blot after oral administration by gavage of 25 mg/kg efavirenz or the corresponding vehicle (corn oil), once daily during five days. The treatment with efavirenz was selected on the basis of a 98.8% reduction of the HIV-1 cDNA load in the spleen of Sprague-Dawley rats (Goffinet et al., 2007). RESULTS: Specific concentration-dependent BCRP expression was observed in spleen, liver,  monocytes, limphocytes and the blood brain barrier. An increase in the BCRP protein abundance was observed in monocytes, limphocytes as well as in the blood brain barrier of efavirenz-treated compared with vehicle-treated animals. CONCLUSIONS: Our study demonstrates that efavirenz could modulate BCRP expression which in turn could influence the bioavailability and targeted delivery of this drug to target or sanctuary HIV-sites.