TABLE 4

Pharmacokinetic parameters of zonampanel after i.v. bolus administration of zonampanel (15 mg/kg) with or without probenecid (50 mg/kg) or cimetidine (40 mg/kg) to rats Values in parentheses represent the ratio to the respective control group.


Parameter

Probenecid

Cimetidine
Control Group
Coadministered Group
Control Group
Coadministered Group
Ae 0→3 ha (% of dose) 77.7 ± 2.6 85.5 ± 3.0 67.4 ± 12.1 75.7 ± 4.0
Ae 0→6 ha (% of dose) 77.8 ± 3.9 76.2 ± 6.0 77.2 ± 3.1 79.3 ± 2.0
C0 (μg/ml) 57.8 95.1 (165%) 73.5 102 (139%)
AUClast (μg · min/ml) 584 1691 (290%) 686 1090 (158%)
AUCinf (μg · min/ml) 584 1690 (290%) 686 1090 (158%)
t1/2 (min) 13.0 14.1 (108.7%) 16.6 14.1 (84.8%)
Vss (ml/kg) 236 151 (63.8%) 211 159 (75.6%)
CLtot, p (ml/min/kg) 25.7 8.9 (34.5%) 21.9 13.8 (63.2%)
CLtot, b (ml/min/kg) 40.1 13.9 (34.5%) 34.2 21.6 (63.2%)
CLrenal, b (ml/min/kg) 31.2 10.6 (33.8%) 26.4 17.1 (64.9%)
CLnonrenal, b (ml/min/kg) 8.92 3.29 (36.9%) 7.79 4.46 (57.2%)
CLrenal, sr, b (ml/min/kg) 29.0 8.3 (28.8%) 24.1 14.9 (61.7%)
CLrenal, sr, int (ml/min/kg) 210 36.6 (17.4%) 148 73.4 (49.6%)
CLbile, int, all (ml/min/kg)
54.4
17.9 (32.9%)
46.5
24.8 (53.5%)
  • a Values are mean ± S.D. of four individual rats