Effect of various compounds on the hOAT3-mediated uptake of 2 μM sitagliptin and comparison with Cmax
Compound | IC50a | Plasma Cmaxb | References | |
|---|---|---|---|---|
| μM | ||||
| Cimetidine | 79 ± 20 | 7.0 (400 mg) | Van Crugten et al. (1986) | |
| Enalapril | 43 ± 0.1%c | 0.83 (10 mg) | Arafat et al. (2005) | |
| Enalaprilat | >100 | 0.16 (10 mg) | Arafat et al. (2005) | |
| Fenofibrate | >100 | 40 (145 mg) | Gustavson et al. (2006) | |
| Fenofibric acid | 2.2 ± 0.1 | 0.26-0.81d | Yamazaki et al. (2005) | |
| Furosemide | 1.7 ± 0.4 | 5.1 (40 mg) | Hardman and Limbird (2001) | |
| 0.07 (40 mg)d | Hardman and Limbird (2001) | |||
| Gabapentin | >100 | 28 (400 mg) | Blum et al. (1994) | |
| Ibuprofen | 3.7 ± 0.3 | 135 (400 mg) | Albert and Gernaat (1984) | |
| 0.7 (400 mg)d | Albert and Gernaat (1984) | |||
| Indapamide | 11 ± 1.7 | 0.91 (5 mg)e | Grebow et al. (1982) | |
| Probenecid | 5.6 ± 1.4 | 12 to 44 (0.5 to 2 g)d | Selen et al. (1982) | |
| Quinapril | 6.2 ± 1.7 | 1.31 (20 mg)f | Breslin et al. (1996) | |
↵ a hOAT3-mediated sitagliptin uptake was examined by subtracting sitagliptin uptake in control cells from that in hOAT3-transfected cells. The IC50 value for inhibition by the compounds tested was obtained by fitting the data to eq. 4 by nonlinear regression analysis using KaleidaGraph.
↵ b Maximal total concentration in plasma, unless otherwise indicated; the number in parentheses represents the clinical dose.
↵ c Percentage of control at 100 μM enalapril.
↵ d Maximal concentration of unbound drug.
↵ e Maximal total concentration in blood.
↵ f Maximal total concentration of active carboxylic acid.