TABLE 5.
Maternal pyrazinamide dose, pharmacokinetic parameters, and target attainment a
| Median value for group (IQR) | 2T/PP comparison b | 3T/PP comparison b | |||||
|---|---|---|---|---|---|---|---|
| Second trimester n = 6 |
Third trimester n = 9 |
Postpartum n = 2 |
GMR (90% CI) | P-value | GMR (90% CI) | P-value | |
| Dose (mg/kg) | 22.75 (21.58–26.18) | 25.00 (21.70–26.03) | 22.29 (20.83–23.74) | – | – | – | – |
| AUC0–24 (µg·h/mL) | 373.73 (340.25–560.14) | 404.69 (389.42–432.82) | 388.30 (370.85–405.74) | 1.03 (0.51–2.07) | 0.928 | 1.12 (0.61–2.04) | 0.650 |
| CL/F (L/h) | 3.55 (3.25–3.98) | 3.55 (2.77–3.79) | 4.01 (3.70–4.31) | 0.90 (0.63–1.27) | 0.453 | 0.84 (0.58–1.20) | 0.282 |
| T max (h) | 2 (1–4) | 2 (1–4) | 2 (2) | – | – | – | – |
| T ½ (h) | 8.40 (7.08–9.34) | 8.32 (7.60–9.49) | 7.85 (7.77–7.94) | 1.07 (0.76–1.50) | 0.630 | 1.13 (0.78–1.65) | 0.440 |
| C max (µg/mL) | 35.55 (28.80–46.70) | 33.80 (32.10–39.60) | 35.05 (33.20–36.90) | 1.04 (0.64–1.70) | 0.831 | 1.10 (0.62–1.95) | 0.669 |
| C 0 (µg/mL) | 4.01 (3.57–6.06) | 5.08 (3.98–5.72) | 4.53 (4.51–4.55) | 1.03 (0.35–3.04) | 0.935 | 1.10 (0.40–3.06) | 0.812 |
| C 12 (µg/mL) | 13.25 (12.40–21.40) | 15.00 (14.00–17.90) | 13.90 (13.20–14.60) | 1.02 (0.45–2.34) | 0.941 | 1.14 (0.55–2.37) | 0.647 |
| n (%) C max <20 µg/mL target | 0 (0) | 0 (0) | 0 (0) | – | – | – | – |
| n (%) AUC0–24 <363 µg·h/mL target | 2 (33) | 2 (22) | 0 (0) | – | – | – | – |
a
Summary statistics for second/third trimester and postpartum presented as median (IQR), except T max, which is presented as median (range). AUC0-24: area under the concentration versus time curve over the dosing interval; CL/F: apparent oral clearance; T max: time to maximum plasma concentration; t 1/2: half-life; C max: maximum plasma concentration; C 0: pre dose concentration; C 12: 12h post-dose concentration.
b
Comparisons between pregnancy and postpartum presented as univariate mixed-effect model GMRs with a 90% confidence interval and P-value.