TABLE 2

Pharmacokinetic parameter estimates of the base model and final model and bootstrap estimates of the final model

ParameteraPopulation estimateBootstrap estimatebPrecision (RSE)d
Base modelFinal model
Structural model
    CL/F (liters/h)50.830.230.69.9
    V/F (liters)2,0901,1001,11012.8
    ka (h−1)1.331.261.2928.4
    Absorption lag time (h)1.791.791.819.2
IIV and IOV
    IIV CL/F (% CV)58.146.445.89.17
    IIV V/F (% CV)73.830.229.632.3
    IIV ka (% CV)46.853.45733.4
    IOV F (% CV)28.623.623.713.4
    F, volunteers vs patientsc257%123%126%26.5
Residual variability
    Proportional error, study 1 (% CV)6.976.766.774.37
    Proportional error, study 2 (% CV)62.753.852.88.34
  • a ka, first-order absorption rate constant; CL/F, apparent clearance; V/F, apparent volume of distribution; F, bioavailability.

  • b Data obtained from nonparametric bootstrap analysis (200 data sets).

  • c Difference in bioavailability in healthy volunteers versus patients.

  • d RSE, relative standard error, expressed as a percentage.