Sulfasalazine and sulfapyridine pharmacokinetic parameters in SAGE knockout rats
Data are means ± S.D. n = 4 to 8.
| Parameter | Wild Type | Bcrp KO | Mdr1a KO | Mrp2 KO |
|---|---|---|---|---|
| Sulfasalazine (5 mg/kg i.v.) | ||||
| AUCinf, ng · h/ml | 8401 ± 1923 | 10,727 ± 1088* | 6260 ± 785 | 4320 ± 1772* |
| CL, ml · min−1 · kg−1 | 10.4 ± 2.5 | 7.8 ± 0.8 | 13.5 ± 1.9 | 22.0 ± 8.2 |
| VD, SS, ml/kg | 168 ± 47 | 408 ± 142* | 285 ± 62* | 1298 ± 499* |
| t1/2, h | 1.6 ± 1.3 | 1.4 ± 0.5 | 1.0 ± 0.3 | 4.3 ± 0.7* |
| Sulfasalazine (20 mg/kg p.o.) | ||||
| AUCinf, ng · h/ml | 562 ± 247 | 13,104 ± 6522* | 711 ± 338 | 635 ± 181 |
| Cmax, ng/ml | 185 ± 74 | 3872 ± 1600* | 213 ± 65 | 320 ± 392 |
| Tmax, h | 0.25 ± 0.00 | 0.6 ± 0.6 | 0.3 ± 0.1 | 0.25 ± 0.00 |
| t1/2, h | 2.6 ± 1.2 | 1.9 ± 0.9 | 2.3 ± 1.1 | 3.8 ± 1.1 |
| F, % | 1.4 ± 0.7 | 30 ± 15* | 2.8 ± 1.2 | 4.0 ± 1.7* |
| Sulfapyridine (20 mg/kg sulfasalazine p.o.) | ||||
| M/P | 50 ± 29 | 4.6 ± 10.2* | 24 ± 15 | 22 ± 8 |
| AUCinf, ng-eq · h/ml | 21,992 ± 3398 | 14,576 ± 10,009 | 14,985 ± 5891 | 12,675 ± 1198* |
| Cmax, ng-eq/ml | 4764 ± 1777 | 2843 ± 2135 | 2525 ± 1218 | 2499 ± 368* |
| Tmax, h | 5.0 ± 1.9 | 4.0 ± 0.0 | 7.0 ± 2.0 | 4.4 ± 2.2 |
| t1/2, h | 2.3 ± 0.8 | 1.7 ± 0.7 | 1.3 ± 0.5 | 1.6 ± 0.7 |
KO, knockout; AUCinf, area under the curve extrapolated to infinity; CL, clearance; VD, SS, volume of distribution; t1/2, half-life; Cmax, maximum concentration; Tmax, time to maximum concentration; F, bioavailability; M/P, metabolite/parent ratio.
↵* p < 0.05.