In vitro and in vivo inhibition of Pgp and BCRP by tariquidar and elacridar as shown in representative studies
| Model Used | Tariquidar | Elacridar | References | |||
|---|---|---|---|---|---|---|
| Pgp | Bcrp | Pgp | Bcrp | |||
| In vitro assays | Flow cytometry in a mitoxantrone efflux assay (BCRP) and a calcein-AM efflux assay (Pgp) | 223 nM (IC50) | 916 nM (IC50) | 193 nM (IC50) | 250 nM (IC50) | (Kühnle et al., 2009) |
| Loperamide uptake in LMDR1 cells (Pgp) | 15 nM (IC50) | (Choo et al., 2006) | ||||
| Hoechst 33342 assay using MCF-7 MX cells (BCRP) and A2780adr cells (Pgp) | 72 nM (IC50) | 1445 nM (IC50) | (Pick et al., 2008) | |||
| In vivo models | PET studies with (R)-[11C]-verapamil in rats | 3 mg/kg (ED50) | 1.2 mg/kg (ED50) | (Kuntner et al., 2010) | ||
| Brain uptake of loperamide in mice | 5.65 mg/kg (ED50) | 2.36 mg/kg (ED50) | (Choo et al., 2006) | |||
| Rhodamine 123 efflux in CD3e lymphocytes of inhibitor treated mice | 0.25 mg/kg (ED50) | 1.34 mg/kg (ED50) | (Choo et al., 2006) | |||
BCRP, breast cancer resistance protein; ED50, half-maximum effect dose; IC50, half-maximum inhibitory concentration; PET, positron emission tomography; Pgp, P-glycoprotein.