FIG 5.

Raltegravir accumulation and permeability in Caco-2 cells: interactions with ABC transporters. (A) Time profile of [³H]raltegravir in Caco-2 cells. The uptake of 1 μM [³H]raltegravir by the Caco-2 confluent monolayer cells was measured over time at 37°C. The inset shows the linearity of initial uptake up to 2 min. (B) Accumulation of 1 μM [³H]raltegravir (120 min) by Caco-2 cells in the absence or presence of inhibitors of P-gp (5 μM PSC833), BCRP (5 μM Ko143), or MRPs (5 μM MK571). (C) Raltegravir intestinal permeability across Caco-2 monolayer cells in the apical-to-basolateral and basolateral-to-apical directions. The flux of raltegravir was determined by introducing 1 μM [³H]raltegravir into the donor compartment (apical or basolateral) and measuring its appearance over time in the receiver compartment (basolateral or apical, respectively) in the absence or presence of 5 μM PSC833 or 5 μM Ko143 to calculate the apparent permeability coefficients (P_app). The results are expressed as the mean ± SEM from at least three independent experiments, with each data point in an individual experiment representing triplicate measurements. Statistical significance was assessed applying the one-way ANOVA, followed by Bonferroni's correction for a test of repeated measures. *, P < 0.05.