4.1.3  BCRP
BCRP is a novel ABC-transporter which is localised in various tissues including cerebral endothelial cells (Eisenblatter et al., 2003). It is believed to have a similar tissue localisation to P-gp (Fig. 1). PIs such as ritonavir, saquinavir and nelfinavir have found to be effective inhibitors, but not substrates of this transporter (Gupta et al., 2004). Studies have also found that BCRP is a cellular factor involved in the resistance to NRTIs. For example, the accumulation and anti-HIV activity of AZT was significantly reduced by diminishing its metabolites, in cells overexpressing BCRP and this was reversed by fumitremorgin C, a BCRP inhibitor, suggesting that AZT is a substrate of BCRP (Wang and Baba, 2005; Wang et al., 2004).
More recently, a murine homolog of human BCRP was used to investigate the contribution of BCRP in the directional transport of abacavir and AZT. Their data provided evidence suggesting that both these drugs are substrates for Bcrp1 and further directional transport studies confirmed the role of Bcrp in the polarised transport of both abacavir and AZT in vitro (Pan et al., 2007). However, in vivo results showed that deletion of Bcrp1 has little influence on the brain penetration or overall disposition of AZT and only a moderate effect on abacavir (Giri et al., 2008). Overall, findings from these studies suggest that BCRP could contribute to drug–drug interactions observed in vivo following HAART. The role of this efflux protein during co-administration of anti-HIV drugs that are either substrates, inhibitors or both of BCRP, could be very valuable for the delivery of HAART to viral sanctuary sites.