TABLE 1

Effect of 1-aminobenzotriazole administration on the oral pharmacokinetics of NVS-CRF38 in female Wistar rats.

ABT-treated animals received 100 mg/kg oral ABT dissolved in water; the control animals received an equivalent dose of water. After 2 hours, 10 mg/kg NVS-CRF38, formulated as a suspension in 0.5% methylcellulose and 0.5% Tween 80, was orally administered to all rats. The dose volume for both compound and inhibitor was 5 ml/kg. Plasma samples were taken to 72 hours and analyzed by LC-MS/MS. Data are the mean and standard deviation of four rats.

ParametersOral NVS-CRF38
No InhibitorABT (100 mg/kg)
NVS-CRF38 Parameters
Dose (mg/kg)1010
Tmax (hr)0.9 ± 0.4**37 ± 13
Cmax (nM)8263 ± 8238279 ± 739
AUC0→t (nM•hr)157,107 ± 22,787**390,985 ± 48,100
O-Desmethyl NVS-CRF38 Parameters
Tmax (hr)22 ± 14*60 ± 24
Cmax (nM)428 ± 43**126 ± 38
AUC0→t (nM•hr)15,102 ± 1,577**4,209 ± 1,274

  • ↵* P < 0.05 (Student’s t test) versus values in vehicle-treated group.

  • ↵** P < 0.01 (Student’s t test) versus values in vehicle-treated group.