Table 3.
Pharmacokinetic Parameters for Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol in Children Treated for Tuberculosis
| Median Value (IQR) | ||||
|---|---|---|---|---|
| Parameter | Rifampicin (n = 77) | Isoniazid (n = 76) | Pyrazinamide (n = 45) | Ethambutol (n = 22) |
| AUC24, mg⋅h/La | 32.5 (20.1–45.1) | 16.7 (9.2–25.9) | 317 (263–399) | 9.5 (7.5–11.5) |
| Cmax, mg/L | 7.6 (4.9–11.4) | 5.1 (2.8–7.7) | 33.0 (25.9–43.1) | 1.6 (0.9–2.0) |
| t½, h | 1.7 (1.5–2.3) | 3.2 (2.6–4.2) | 6.3 (5.6–7.5) | 4.4 (3.3–5.7) |
| tmax, h | 2 (1–2) | 1 (1–2) | 1 (1–2) | 2 (2–4) |
| Ke, h−1 | 0.40 (0.30–0.47) | 0.22 (0.16–0.26) | 0.11 (0.09–0.12) | 0.16 (0.12–0.21) |
Abbreviations: AUC24, area under the concentration-time curve from 0 to 24 hours; Cmax, maximum plasma concentration; IQR, interquartile range; Ke, elimination rate constant; t½, elimination half-life; tmax, time to Cmax.
aThe following AUC24 reference values were used. For rifampicin, the estimate AUC24 (38.73 mg⋅h/L) is derived from a systematic review and meta-analysis by Stott et al [22]. For isoniazid, pyrazinamide, and ethambutol, 11.6–26.3, 233–429, and 16–28 mg⋅h/L represent the respective ranges of the medians from studies in a systematic review by Daskapan et al [23]. The target Cmax reference ranges recommended by Alsultan and Peloquin [16] were 8–24 mg/L, 3–6 mg/L, 20–60 mg, and 2–6 mg/L for rifampicin, isoniazid, pyrazinamide, and ethambutol, respectively.