Values used for model simulations and resulting predicted steady-state rosuvastatin concentrations and partitioning
Clearance parameters were scaled from those determined in the in vitro model to represent those in the liver of a 5-kg monkey. Volumes for the extracellular and intracellular compartments were fixed to those of the plasma and liver, respectively, of a 5-kg monkey. Extracellular and intracellular fu were fixed to those measured in monkey plasma and liver, respectively. The initial condition for CEC and CIC was arbitrarily fixed to 1 and 0 µM, respectively.
PSdiff | Clup | fuEC | fuIC | CEC | CIC | Kp | Kpu,u | |
---|---|---|---|---|---|---|---|---|
ml/min | ml/min | µM | µM | |||||
Scaled in vitro model parameters | 82 | 1010 | 0.12 | 0.12 | 0.11 | 1.4 | 12 | 12 |
Corrected for transporter expression | 82 | 1147 | 0.12 | 0.12 | 0.10 | 1.5 | 15 | 15 |
Corrected for cell surface area | 14 | 1010 | 0.12 | 0.12 | 0.011 | 1.6 | 74 | 74 |
Active uptake not limited by binding | 82 | 1010 | 0.12a | 0.12 | 0.015 | 1.6 | 106 | 106 |
EC = extracellular; IC = intracellular.
↵a Removed from Clup.