Fit a two-compartmentx model to a set of measurements (any arbitrary dosing regimen is allowed)
The central compartment is referred to as C, while the peripheral compartment as Cp. The differential equation is V dC/dt = -(Clint+Clp+Cl) * C + Clp * Cp + dD/dt, Vp dCp/dt = Clp * C - Clp * Cp
where C is the concentration of the central compartment, Cl the clearance, V and Vp the distribution volume of the central and peripheral compartment,
Clint is a saturated clearance
Clp is the distribution rate between the central and the peripheral compartments,
Vmax is the maximum processing capability of the metabolic pathway degrading the drug,
Km is the Michaelis-Menten constant,and D the input dosing regime.
Note that the intrinsic clearance occurs at the central volume.
Confidence intervals calculated by this fitting may be pessimistic because it assumes that all model parameters are independent, which are not. Use Bootstrap estimates instead.
Protocol created by http://www.kinestatpharma.com