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. 2020 Feb 21;64(3):e01978-19. doi: 10.1128/AAC.01978-19

TABLE 2.

Final population pharmacokinetic model parameter estimates for isoniazid, pyrazinamide, and ethambutol

Parameter description Typical value (95% CI) fora:
Isoniazid Pyrazinamide Ethambutol
CL for rapid NAT2 acetylators (liters/h)b 97.1 (68.6–144)
CL for intermediate NAT2 acetylators (liters/h)b 75.7 (59.4–95.8) 3.39 (2.96–3.87) 60.2 (53.7–68.5)
CL for slow NAT2 acetylators (liters/h)b 29.0 (24.3–34.8)
V1 (liters)b,c 130 (106-162) 43.8 (39.7–47.2) 268 (154–419)
Q (liters/h)b,c 12.4 (5.64–31.3) 174 (71.7–385)
Vp (liters)b,c 28.5 (10.8–50.1) 334 (217–490)
MTT (h)c 1.21 (0.953–1.51) 0.934 (0.565–1.17) 2.15 (1.84–2.51)
NNc 8.01 (3.95–14.9) 3.78 (2.24–7.71) 6.23 (3.21–11.6)
Bioavailability (F) 1 fixed 1 fixed 1 fixed
Proportional error (%) 22.2 (15.2–30.4) 9.19 (6.99–14.4) 23.3 (17.8–33)
Additive error (mg/liter) 0.045 (0.035–0.062) 0.011 (0.002–0.019) 0.03e fixed
BSV of clearance (%CV)d 12.7 (1.37–30.8) 25.4 (17.1–40.3) 4.69 (0.379–20.4)
BOV of mean transit time (%CV)d 56.7 (43.3–78.0) 71.9 (41.2–125) 24.1 (15.9–36.0)
BOV of bioavailability (%CV)d 36.7 (27.0–48.7) 13.6 (5.81–18.7) 20.1 (10.6–32.2)
a

95% confidence intervals were obtained by the sampling importance resampling technique using PsN software.

b

Allometric scaling was used for the clearance (CL) by fat-free mass (FFM), intercompartmental clearance (Q), central volume of distribution (V1), and peripheral volume of distribution (Vp) (by weight); typical values are reported for the median FFM and median weight as reported in Table 1.

c

Prior values (uncertainty) were added to the parameter estimates, as follows: for isoniazid, the Q (16.1 liters/h [50%]), Vp (16.5 liters [50%]), absorption mean transit time (MTT) (0.924 h [50%]), and number of transit compartments (NN) (2.73 [50%]); for pyrazinamide, the MTT (0.84 h [30%]) and NN (2.6 [50%]); and for ethambutol, the V1 (266 liters [50%]), Vp (687 liters [50%]), Q (109 liters/h [50%]), MTT (2.54 h [50%]), and NN (11.1 [50%]).

d

Between-subject variability (BSV) and between-occasion variability (BOV) were assumed to be log-normally distributed and are reported as approximate %CVs.

e

The estimate of the additive error was not statistically significant from its lower bound (LLOQ/2); thus, it was fixed to that value.