TABLE 4

Pharmacokinetic models useda

Model(s)Differential equation
1 and 4dX(1)/dt = R(t) − [(CLINT + CLSLOPE × CLCR)/Vc + k12] × X(1) + k21 × X(2) and dX(2)/dt = k12 × X(1) − k21 × X(2)
2dX(1)/dt = R(t) − [ke + k12] × X(1) + k21 × X(2); dX(2)/dt = k12 × X(1) − k21 × X(2)
3bdX(1)/dt = R(t) − [CL/(Vc0 · wt)] × X(1) + k21 × X(2); dX(2)/dt = k12 × X(1) − k21 × X(2)
  • a X(1) is the amount of drug in the central compartment, and X(2) is the amount of drug in the peripheral compartment. R(t) is a time-delimited zero-order drug input rate (piecewise input function) into the central compartment (milligrams per hour). CL is the clearance from the central compartment (liters per hour), Vc represents the apparent volume of distribution from the central compartment. and k12 and k21 are first-order intercompartmental transfer rate constants (per hour). ke is the first-order elimination constant (per hour) from the central compartment. See also Table 2, footnote a, for additional definitions.

  • b Model 3 included weight as a linear covariate, such that Vc = Vc0 · weight, where Vc0 was the parameter to be estimated, normalized to weight.