Figure 1.
Molecular structure of ST-246.
Figure 2.
Plots of mean plasma concentration versus time profiles in BALB/c mice following repeat oral administrations of ST-246 by gavage at a dose of 2000 mg/kg for 28 consecutive days.
The adjacent plot represents the corresponding semi-logarithmic plot.
Figure 3.
Plots of mean plasma concentration versus time profiles in New Zealand white Hra: (NZW) SPF albino rabbits following repeat oral administrations of ST-246 by gavage at a dose of 100 mg/kg seven consecutive days.
The adjacent plot represents the corresponding semi-logarithmic plot.
Figure 4.
Plots of mean plasma concentration versus time profiles in cynomolgus monkeys following repeat oral administrations of ST-246 by gavage at a dose of 100 mg/kg for 28 consecutive days.
The adjacent plot represents the corresponding semi-logarithmic plot.
Figure 5.
Plots of mean plasma concentration versus time profiles in beagle dogs, following repeat oral administrations of ST-246 by gavage at a dose of 30 mg/kg seven consecutive days.
The adjacent plot represents the corresponding semi-logarithmic plot.
Table 1.
Plasma pharmacokinetic estimates for BALB/c mice, New Zealand white Hra: (NZW) SPF albino rabbits, beagle dogs and cynomolgus monkeys following repeat oral dosing of ST-246 by gavage for 7 consecutive days in New Zealand white Hra: (NZW) SPF albino rabbits and beagle dogs and 28 consecutive days in BALB/c mice and cynomolgus monkeys.
Table 2.
Plasma pharmacokinetic estimates for BALB/c mice, New Zealand white Hra: (NZW) SPF albino rabbits, beagle dogs and cynomolgus monkeys following repeat oral dosing of ST-246 by gavage for 7 consecutive days in New Zealand white Hra: (NZW) SPF albino rabbits and beagle dogs and 28 consecutive days in BALB/c mice and cynomolgus monkeys.
Figure 6.
Linear regression analysis of log-transformed plasma clearance for BALB/c mice, New Zealand white Hra: (NZW) SPF albino rabbits, cynomolgus monkeys and beagle dogs versus log-transformed corresponding animal body weight, following oral administration of ST-246 by gavage at a dose of 2000, 100, 100 and 30 mg/kg, respectively.
Figure 7.
Linear regression analysis of log-transformed plasma clearance multiplied by corresponding maximum life span potential (MLP) for BALB/c mice, New Zealand white Hra: (NZW) SPF albino rabbits, cynomolgus monkeys and beagle dogs versus log-transformed corresponding animal body weight, following oral administration of ST-246 by gavage at a dose of 2000, 100, 100 and 30 mg/kg, respectively.
Figure 8.
Linear regression analysis of log- transformed apparent volume of distribution for BALB/c mice, New Zealand white Hra: (NZW) SPF albino rabbits, cynomolgus monkeys and beagle dogs versus log-transformed corresponding animal body weight, following oral (gavage) administration of ST-246 by gavage at a dose of 2000, 100, 100 and 30 mg/kg, respectively.
Table 3.
Allometric coefficient, allometric exponent and coefficient of determination values from linear regression analysis of pharmacokinetic parameters from BALB/c mice, New Zealand white Hra: (NZW) SPF albino rabbits, cynomolgus monkeys and beagle dogs following repeat oral administration of ST-246 by gavage for 7 consecutive days in New Zealand white Hra: (NZW) SPF albino rabbits and beagle dogs and 28 consecutive days in BALB/c mice and cynomolgus monkeys.
Table 4.
Observed versus scaled human plasma pharmacokinetics, recommended and given FIH dose levels for ST-246.