TABLE 2

Estimated population PK parameters in the base and final models

ParameteraParameter estimate (RSE [%])bP value
Base modelFinal model
−2LL4,926.14,866.1
Fixed-effect parameters
    Tlag (h)0.333 (10.6)0.326 (1.47)
    ka (h−1)7.25 (34.4)6.61 (17.1)
    V/F (liter)28.5 (4.05)24.9 (2.92)
    βV, wt1.00, fixed
    CL/F (liter/h)1.02 (3.58)2.00 (11.9)
    βCL, patients (vs HS)−0.660 (18.7)<0.0001
    βCL, CrCL0.413 (18.1)<0.0001
Random-effect parameters
    ω, Tlag0.368 (61.5)0.409 (22.5)
    ω, ka1.08 (19.2)1.52 (13.6)
    ω, V/F0.242 (16.7)0.174 (36.6)
    ω, CL/F0.492 (5.59)0.353 (9.29)
    γ, CL/F0.190 (21.1)
Residual error parameter
    Proportional0.202 (3.04)0.190 (3.37)
  • a −2LL, −2 × log-likelihood; β, the estimated effect of the covariate; γ, interoccasion variability; ω, between-subject variability; CL/F, apparent clearance; CrCL, creatinine clearance; HS, healthy subjects; ka, absorption rate constant; SE, standard error; Tlag, lag time; V/F, apparent volume of distribution; wt, body weight.

  • b RSE, relative standard error.