FIG 1.

Raltegravir interactions with ABC transporters. (A) Effect of raltegravir on R-6G accumulation by MDA-MDR1 (P-gp) monolayer cells. The cellular accumulation of R-6G (1 μM) was determined at 60 min by exposing confluent MDA-MDR1 (P-gp) cells to R-6G in assay buffer with or without the P-gp inhibitor CsA (25 μM) or raltegravir (10 to 500 μM). (B) Effect of raltegravir on [³H]mitoxantrone accumulation by HEK-ABCG2-overexpressing cells. The accumulation of [³H]mitoxantrone (20 nM) at 120 min was measured in the absence (control) or presence of BCRP inhibitor (5 μM Ko143) or raltegravir (10 to 100 μM), all in the presence of 2 μM PSC833. (C) Effect of raltegravir on BCECF accumulation by HeLa-MRP1 monolayer cells. The cellular accumulation (at 120 min) of BCECF was determined by exposing confluent HeLa-MRP1 cells to 5 μM BCECF-AM, with or without the MRP inhibitor MK571 (10 μM) or raltegravir (10 to 500 μM), all in the presence of 2 μM PSC833. The results are expressed as the mean ± standard error of the mean (SEM) from at least three independent experiments, with each data point in an individual experiment representing triplicate measurements. Statistical significance was assessed by applying the unpaired two-tailed Student's t test analysis. *, P < 0.05.