TABLE 4

Parameter estimates of the final population pharmacokinetic models for pyrazinamide and ethambutola

DrugParameterbEstimate (RSE, %)IIV (% CV)
PyrazinamideMTT (h)0.33 (9)0.443 (46.6)
Ktr (h−1)12.5 (11)0.455 (48.0)
N3.13
ka (h−1)5.28 (7)2.05 (811.5)
V/F (liters)13.1 (4)0.37 (38.3)
Exponent (BW on V/F)0.677 (11)Fixed
CL/F (liters/h)1.6 (4)0.385 (40.0)
Exponent (BW on CL/F)0.735 (10)Fixed
Constant a0.268 (23)
Slope b0.112 (7)
EthambutolTlag (h)0.723 (7)0.174 (17.5)
Tk0 (h)0.9 (16)0.605 (66.5)
CL/F (liters/h)32.5 (5)0.458 (48.3)
Exponent (BW on CL/F)0.382 (24)Fixed
V1/F (liters)112 (7)0.607 (66.7)
Exponent (BW on V1/F)0.228 (84)Fixed
Q/F (liters/h)15.4 (10)0.274 (27.9)
Exponent (BW on Q/F)0.474 (44)Fixed
V2/F (liters)97.8 (8)0.31 (31.8)
Exponent (BW on V2/F)0.858 (60)Fixed
Slope b0.272 (6)
  • a All pharmacokinetic parameters are expressed as median (relative standard error [RSE]). IIV, interindividual variability; CV, coefficient of variability; BW, body weight. MTT, mean transit time.

  • b The residual error modes used in this study consist of the slope b and constant a. The equations are y = f + bfε (proportional) and y = f + (a + bf) ε (combined 1), where f is the structural model and ε is the residual error standardized by Gaussian random variables. The mean transit time was calculated as follows: MTT = (N + 1)/Ktr, where N and Ktr represent the number of compartments and transit rate constant, respectively.