TABLE 3.
Maternal isoniazid dose, pharmacokinetic parameters, and target attainment a
| Median value for group (IQR) | 2T/PP comparison b | 3T/PP comparison b | |||||
|---|---|---|---|---|---|---|---|
| Second trimester n = 14 |
Third trimester n = 19 |
Postpartum n = 12 |
GMR (90% CI) | P-value | GMR (90% CI) | P-value | |
| Dose (mg/kg) | 4.82 (4.16–5.45) | 4.88 (4.07–5.45) | 4.70 (4.44–5.36) | – | – | – | – |
| AUC0–24 (µg·h/mL) | 14.18 (9.41–20.70) | 12.87 (9.29–21.05) | 19.36 (9.58–26.90) | 0.82 (0.69–0.97) | 0.055 | 0.75 (0.65–0.86) | 0.002 |
| CL/F (L/h) | 21.81 (12.08–31.90) | 19.03 (12.63–27.84) | 15.52 (10.00–31.31) | 1.25 (1.08–1.46) | 0.019 | 1.39 (1.22–1.57) | <0.001 |
| T max (h) | 1 (1, 2) | 1 (1, 2) | 1 (1, 2) | – | – | – | – |
| T ½ (h) | 2.19 (1.49–2.75) | 2.93 (1.61–3.31) | 2.92 (1.51–3.34) | 0.83 (0.69–0.98) | 0.074 | 0.96 (0.83–1.12) | 0.668 |
| C max (µg/mL) | 4.23 (3.42–5.14) | 3.32 (2.18–4.60) | 3.89 (3.09–6.01) | 0.91 (0.72–1.16) | 0.519 | 0.77 (0.63–0.95) | 0.044 |
| C 0 (µg/mL) | BQL (BQL–BQL) | BQL (BQL–BQL) | BQL (BQL–BQL) | – | – | – | – |
| C 12 (µg/mL) | 0.09 (BQL–0.26) | 0.28 (BQL −0.38) | 0.30 (BQL −0.62) | – | – | – | – |
| n (%) C max <3 µg/mL target | 3 (21) | 6 (32) | 3 (25) | – | – | – | – |
| n (%) AUC0–24 <10.52 µg·h/mL target | 4 (29) | 5 (26) | 3 (25) | – | – | – | – |
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: 12 hours post-dose concentration; BQL: below quantification limit.
b
Comparisons between pregnancy and postpartum presented as univariate mixed-effect model GMR with a 90% confidence interval and P-value. Values in italic type are significant P-values (<0.1).