Table 2.
Final PK parameter estimates for isoniazid
| Parameter | Typical value (95% CI a ) | Variability b , %CV (95% CI a ) |
|---|---|---|
| CLint c , L/hour, NAT2 rapid | 72.3 (61.5–86.7) | 69.2 (64.2–74.2) e |
| CLint c , L/hour, NAT2 intermediate | 38.5 (34.6–43.2) | |
| CLint c , L/hour, NAT2 slow | 14.5 (13.1–16.0) | |
| V c d , L | 37.6 (33.9–40.7) | |
| V p d , L | 13.3 (10.5–16.9) | |
| Q/F c , L/hour | 3.32 (2.53–4.54) | |
| k a, 1/hour | 2.69 (1.91–3.51) | 145 (116–172) f |
| MTT, hours | 0.342 (0.209–0.459) | 116 (98.7–150) f |
| NN | 48.4 (22.2–83.8) | |
| QH c , L/hour | 90 FIXED | |
| fu, % | 95 FIXED | |
| Prehepatic relative bioavailability | 1 FIXED | 12.3 (8.20–15.7) f |
| Proportional error, % | 13.2 (11.3–15.3) | |
| Additive error, mg/L | 0.0378 (0.0335 −0.0449) | |
| Pregnancy effect on CL, % | +26.2 (19.8–33.2) |
%CV, percent coefficient of variation; CI, confidence interval; CL, clearance; CLint, clearance intrinsic; f u, unbound fraction of isoniazid in plasma 50; INH, isoniazid; k a, first‐order rate constant of INH absorption; MTT, absorption mean transit time; NN, number of absorption transit compartment; PK, pharmacokinetic; Q/F, apparent intercompartmental clearance for INH; QH, blood liver flow 40; Vc, apparent central volume of distribution for INH; Vp, apparent peripheral volume of distribution for INH.
The bold values represent significant covariates in the models.
The 95% CIs were obtained with the Standardized Infection Ratio procedure.
Variability was modeled with log‐normal distribution and is presented as an approximate percentage CV.
Clearance parameters are allometrically scaled based on fat‐free mass (typical value reported for 39 kg, which was the median fat‐free mass weight of the study population).
Volume of distribution parameters are scaled based on weight (typical value reported for 67 kg, which was the median weight of the study population).
Between subject variability.
Between occasion variability.