Sumatriptan | Fenoterol | Ondansetron | Tropisetron | |||||
---|---|---|---|---|---|---|---|---|
WT | KO | WT | KO | WT | KO | WT | KO | |
Clblood (ml/kg per minute) | 45.0 (8.1) | 29.0 (6.5)** | 26.7 (4.3) | 13.3 (1.6)*** | 82.7 (18) | 64.5 (16)** | 118 (17) | 96.6 (13)*** |
1.6 | 2.0 | 1.3 | 1.2 | |||||
Vdss (ml/kg) | 1300 (300) | 1170 (301) | 9380 (4100) | 4300 (2700)* | 2140 (577) | 2100 (670) | 3150 (530) | 3300 (427) |
2.2 | ||||||||
t1/2 (min) | 35.3 (3.2) | 46.6 (15.6) | 440 (260) | 442 (250) | 23.6 (4.0) | 25.9 (4.4) | 30.0 (5.0) | 34.8 (5.6)* |
0.86 | ||||||||
Clrenalblood (ml/kg per minute) | 19 | 23 | 10 | 6.6 | NC | NC | 22.3 | 26.7 |
0.83 | 1.5 | 0.82 | ||||||
Fold fublood × GFR | 2.3 | 2.8 | 8.9 | 5.4 | 8.6 | 10.3 | ||
Cl hepaticblood (ml/kg per minute) | 26 | 6.0 | 17 | 6.7 | 83 | 65 | 96 | 69 |
4.3 | 2.5 | 1.3 | 1.4 | |||||
AUCpo0-∞ (nM × h) | 2010 (556) | 3610 (631)*** | 392 (71) | 2340 (1040)** | 2040 (850) | 2700 (737) | 831 (166) | 1210 (264)*** |
0.56 | 0.17 | 0.68 | ||||||
Cmax (ng/ml) | 286 (120) | 439 (160) | 45.5 (17) | 333 (125)*** | 553 (260) | 692 (215) | 545 (189) | 704 (260) |
0.14 | ||||||||
F | 0.30 | 0.36 | 0.029 | 0.10 | 0.28 | 0.30 | 0.33 | 0.37 |
Fh | 0.79 | 0.95 | 0.86 | 0.95 | 0.30 | 0.46 | 0.23 | 0.45 |
FaFg | 0.38 | 0.38 | 0.034 | 0.11 | 0.76 | 0.60 | 1.00 | 0.89 |
B:P | 0.98 (0.10) | 1.05 (0.26) | 8.75 (0.97) | 7.87 (0.26) | 0.93 (0.07) | 0.94 (0.05) | 1.55 (0.03) | 1.56 (0.03) |
AUCpo0–∞, area under the blood concentration–time curve (following oral administration, calculated from 0 to infinity); B:P, blood-to-plasma ratio; Cl, clearance (following intravenous administration); Cmax, maximum plasma concentration (following oral administration); fublood × GFR, fuplasma/B:P × glomerular filtration rate in mice (fuplasma determined in-house); KO, Oct1/2 knockout; NC, not calculated (<10% dose); t1/2, blood half-life (following intravenous administration); Vdss, steady-state volume of distribution (following intravenous administration); WT, wild type.
↵* P < 0.05 using Student’s t test, compared with WT.
↵** P < 0.01 using Student’s t test, compared with WT.
↵*** P < 0.001 using Student’s t test, compared with WT.