TABLE 4.
Maternal ethambutol dose, pharmacokinetic parameters, and target attainment a
| Median value for group (IQR) | 2T/PP comparison b | 3T/PP comparison b | |||||
|---|---|---|---|---|---|---|---|
| Second trimester n = 8 |
Third trimester n = 11 |
Postpartum n = 4 |
GMR (90% CI) | P-value | GMR (90% CI) | P-value | |
| Dose (mg/kg) | 16.85 (15.40–17.67) | 16.37 (14.92–18.86) | 16.49 (15.10–17.03) | – | – | – | – |
| AUC0–24 (µg·h/mL) | 13.77 (12.86–17.08) | 14.53 (12.57–16.87) | 23.55 (22.35–24.68) | 0.59 (0.41–0.85) | 0.032 | 0.61 (0.44–0.86) | 0.032 |
| CL/F (L/h) | 72.72 (61.61–85.56) | 73.75 (65.65–75.75) | 45.43 (42.59–49.15) | 1.57 (1.36–1.80) | 0.001 | 1.51 (1.32–1.74) | 0.002 |
| T max (h) | 4 (2–4) | 4 (2–4) | 4 (2–6) | – | – | – | – |
| T ½ (h) | 3.90 (3.51–4.70) | 4.04 (3.16–4.31) | 4.08 (3.76–4.67) | 0.96 (0.74–1.24) | 0.752 | 0.93 (0.73–1.19) | 0.576 |
| C max (µg/mL) | 1.91 (1.60–2.64) | 2.10 (1.67–2.93) | 2.77 (2.65–2.87) | 0.75 (0.58–0.98) | 0.083 | 0.82 (0.63–1.06) | 0.180 |
| C 0 (µg/mL) | 0.17 (0.13–0.20) | 0.15 (0.13–0.17) | 0.29 (0.26–0.38) | 0.50 (0.37–0.69) | 0.007 | 0.51 (0.38–0.69) | 0.007 |
| C 12 (µg/mL) | 0.41 (0.33–0.48) | 0.38 (0.27–0.46) | 0.71 (0.69–0.77) | 0.64 (0.55–0.75) | 0.002 | 0.60 (0.52–0.70) | 0.001 |
| n (%) C max <2 µg/mL target | 4 (50) | 3 (27) | 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: 12 hours post-dose concentration.
b
Comparisons between pregnancy and postpartum presented as univariate mixed-effect model GMRs with a 90% confidence interval and P-value. Values in italic type are significant P-values (<0.1).