TABLE 1

Pharmacokinetic parameters of RSV and RSV lactone after single intravenous (1 mg/kg) or oral (3 mg/kg) administration of RSV to cynomolgus monkeys with and without oral administration of rifampin (18 mg/kg)

Each value represents the mean ± S.E. from 4–10 monkeys.

CompoundRSV i.v.RSV PO
ControlRIF PORatioControlRIF PORatio
RSV
 CLtotal (l/h/kg)1.17 ± 0.170.42 ± 0.03a0.36
Vss(l/kg)1.56 ± 0.271.11 ± 0.240.71
 t1/2 (h)2.93 ± 0.885.85 ± 1.481.9912.99 ± 3.689.36 ± 2.080.72
 AUC0–last (h⋅µM)1.80 ± 0.234.77 ± 0.44a2.650.39 ± 0.212.39 ± 0.54a6.05
 AUCinf (h⋅µM)1.88 ± 0.244.99 ± 0.40a2.660.56 ± 0.272.72 ± 0.55a4.85
Cmax (µM)0.04 ± 0.020.45 ± 0.11a10.30
Tmax (h)4.27 ± 0.631.25 ± 0.40a0.29
 Fh0.270.742.70
 F0.100.484.85
 FaFg0.360.661.80
RSV lactone
 T1/2 (h)1.62 ± 0.111.38 ± 0.090.8514.29 ± 2.696.98 ± 1.10a0.49
 AUC0–last (h⋅µM)1.43 ± 0.233.10 ± 0.31a2.161.39 ± 0.456.33 ± 2.764.56
 AUCinf (h⋅µM)1.50 ± 0.233.16 ± 0.29a2.112.23 ± 0.938.17 ± 3.113.67
 Cmax (µM)1.03 ± 0.333.05 ± 0.31a2.960.11 ± 0.030.83 ± 0.25a7.72
 Tmax (h)0.25 ± 0.000.25 ± 0.001.005.00 ± 0.822.50 ± 0.96a0.50
  • a Significantly different from control group (P < 0.05).