Table 2

Summary of pharmacokinetic (PK) parameters of isoniazid, rifampicin and pyrazinamide among Indonesian children treated for TBM

PK parametersFirst PK assessment (n=20)Second PK assessment (n=12)P value*
Isoniazid
 AUC0–24 (h∙mg/L)18.5 (5.1–47.4)14.5 (5.9–44.2)0.888
 C max (mg/L)4.6 (1.0–10.0)4.7 (2.5–13.6)0.366
 C CSF0–2 (mg/L)†1.4 (0.5–6.1)1.6 (1.2–2.5)n/a
 C CSF3–5 (mg/L)†1.6 (0.3–5.0)1.7 (0.6–5.0)n/a
 C CSF6–8 (mg/L)†1.3 (1.2–4.3)2.3 (1.9–2.8)n/a
Rifampicin
 AUC0–24 (h∙mg/L)66.9 (21.7–118.6)71.8 (36.1–116.5)0.442
 C max (mg/L)9.4 (2.9–23.7)10.4 (5.7–23.3)0.499
 C CSF0–2 (mg/L)†0.2 (0.1–0.4)0.1 (0.1–0.1)n/a
 C CSF3–5 (mg/L)†0.3 (0.1–0.8)0.1 (0.1–0.3)n/a
 C CSF6–8 (mg/L)†0.4 (0.1–1.4)0.2 (0.1–0.7)n/a
Pyrazinamide
 AUC0–24 (h∙mg/L)315.5 (100.6–599.0)328.4 (143.3–1477.7)0.482
 C max (mg/L)37.7 (15.9–61.7)40.5 (22.7–88.4)0.350
 C CSF0–2 (mg/L)†24.4 (11.1–54.9)25.6 (21.3–37.1)n/a
 C CSF3–5 (mg/L)†30.0 (19.2–43.3)24.7 (15.9–38.1)n/a
 C CSF6–8 (mg/L)†19.6 (7.2–37.7)39.4 (23.1–70.8)n/a

  • Data are presented as geometric mean (range). The first PK assessment was performed on day 2 of treatment and the second PK assessment was performed on day 10 of treatment.

  • *Paired-sample t-test on log-transformed data of 12 patients for whom PK data were available both at the first and second PK assessments.

  • †At the first PK assessment, 6, 7 and 7 CSF samples for each drug were available at 0–2 hours, 3–5 hours and 6–8 hours, respectively; and at the second PK assessment, 4, 4 and 3 CSF samples for each drug were available at 0–2 hours, 3–5 hours and 6–8 hours, respectively.

  • AUC0–24, area under the plasma concentration–time curve from 0 to 24 hours postdose; C CSF0–8, drug concentration in cerebrospinal fluid during 0–8 hours postdose; C max, peak plasma concentration; n/a, non-applicable; TBM, tuberculous meningitis.