Figure 4
Plasma profiles and excretion of indoxyl sulfate in wild-type and Abcg2-knockout mice with chronic kidney dysfunction. (a) Plasma concentration-time profiles of deuterium-labeled indoxyl sulfate (d4-IS) in wild-type (WT)-CKD (open circles) and Abcg2-knockout (KO)-CKD (closed circles) mice. Symbols and bars indicate mean and S.E., respectively (n = 4). KO-CKD mice showed significantly longer t1/2 (206.4 ± 104.1 min vs. 48.3 ± 25.0 min, P < 0.05) and higher AUCinf (5.89 ± 2.95 mM·min vs. 1.67 ± 0.74 mM·min, P < 0.05) compared with those of WT-CKD mice. (b) Cumulative excreted amounts of d4-IS (% of dose) via the kidney, biliary tract, and intestine until 30 min after intravenous administration to WT-CKD and KO-CKD mice. Open and closed columns indicate data corresponding to WT-CKD and KO-CKD mice, respectively. Data are presented as mean ± S.E. (n = 5–9). *P < 0.05 (unpaired Student’s t-test). (c) Apparent clearance of d4-IS in each excretion pathway. Closed, open, and shaded columns indicate urinary, biliary, and intestinal excretion clearances, respectively. Clearances were calculated by dividing the cumulative excreted amount of d4-IS (0–30 min) by the plasma AUC of d4-IS (0–30 min) and normalized by the body weight (BW).
