Table 2.
Rifampicin Pharmacokinetic Data by Treatment Arm
| IV-20 | PO-35 | Control | P valuea | |
|---|---|---|---|---|
| AUC0–8 (h × mg/l)b | ||||
| n observationsc | 19 | 19 | 20 | |
| Geometric mean (95% CI) | 163 (142–186) | 162 (129–203) | 30.5 (21.7–42.8) | <.001 |
| Ratio to control | 5.33 | 5.31 | … | |
| P valued | <.001 | <.001 | … | |
| AUC0_24 (h × mg/l)e | ||||
| n observations | 19 | 19 | 21 | |
| Geometric mean (95% CI) | 249 (202–306) | 327 (248–430) | 42.9 (29.2–63.0) | <.001 |
| Ratio to control | 5.80 | 7.62 | … | |
| P valued | <.001 | <.001 | … | |
| Cmax (mg/L)b | ||||
| n observationsg | 19 | 16 | 17 | |
| Geometric mean (95% CI) | 36.2 (31.8–41.2) | 29.3 (23.0–37.5) | 6.04 (4.20–8.68) | <.001 |
| Ratio to control | 5.99 | 4.86 | … | |
| P valued | <.001 | <.001 | … | |
| n (%) achieving TDM target of >8 mg/L | 20 (100) | 20 (100) | 10 (47.62) | <.0001f |
| Tmax (hours) | ||||
| Median (range) | 2.35 (1.83–3.85) | 4.05 (2.17–7.33) | 2.83 (2.08– 8.25) | .002g |
| CCSF (mg/L) | ||||
| n observations | 15 | 19 | 18 | |
| Geometric mean (95% CI) | 1.74 (1.20–2.53) | 2.17 (1.64–2.86) | .27 h (.17– .45) | .058 |
| Ratio to control | 6.44 | 8.00 | … | |
| P valued | <.001 | <.001 | ||
| n (%) with detectable CSF level | 15 (100) | 19 (100) | 8 (44) | <.001 f |
| n (%) with concentration above rifampicin MIC (1 mg/L) | 14 (93.3%) | 18 (94.7%) | 2 (11.1%) | <.001 f |
| Median (IQR) hours post-dose | 4.70 (3.28–5.92) | 4.55 (3.08–6.20) | 4.83 (3.78–5.5) |
Abbreviations: AUC, area under the curve; CI, confidence interval; CSF, cerebrospinal fluid; IQR, interquartile range; MIC, minimum inhibitory concentration; PK, pharmacokinetics; TDM, therapeutic drug monitoring.
a Likelihood ratio P value from general linear regression.
b Standard 2-step noncompartmental analysis on Phoenix WinNonLin. Where concentration was still increasing at the last sampling point it was not possible to determine Cmax.
c AUC0–8 was based on AUC0-last if Tlast was sufficiently close to 8 hours.
d Pairwise comparison between experimental arm and control arm from general linear regression
e AUC0–24 derived using published population PK model in NONMEM [27]
fP value by χ 2 test.
gP value by Kruskal Wallis test.
h 10 participants had CSF levels below the lower limit of quantification (LLOQ = 0.25mg/l). A value of 50% of the LLOQ was assigned.