Table 2.
Mean (±SD) pharmacokinetic parameters and within-subject comparisons for total and unbound rilpivirine during pregnancy and postpartum
| Parameter | Second trimester | Third trimester | Postpartum | LS mean ratio (90% CI) (%) | |
|---|---|---|---|---|---|
| Second trimester versus postpartum | Third trimester versus postpartum | ||||
| Total rilpivirine | |||||
| n | 15 | 13 | 11 | 15 versus 11 | 13 versus 11 |
| C0h (ng/mL) | 75.6 ± 36.2 | 78.0 ± 39.1 | 127 ± 97.0 | ND | ND |
| Cmin (ng/mL) | 54.3 ± 25.8 | 52.9 ± 24.4 | 84.0 ± 58.8 | 64.82 (51.62–81.39)a | 57.61 (45.81–72.45)a |
| Cmax (ng/mL) | 121 ± 45.9 | 123 ± 47.5 | 167 ± 101 | 79.47 (63.21–99.91) | 79.99 (63.36–100.99) |
| tmax (h)b | 4.00 (1.00–9.00) | 4.00 (2.00–24.93) | 4.00 (2.03–25.08) | ND | ND |
| AUC24h (ng·h/mL) | 1792 ± 711 | 1762 ± 662 | 2714 ± 1535 | 70.83 (55.23–90.83) | 69.27 (53.80–89.18) |
| Unbound rilpivirine | |||||
| n | 15 | 13 | 11 | 15 versus 11 | 13 versus 11 |
| Cmin (ng/mL) | 0.144 ± 0.0676 | 0.148 ± 0.0706 | 0.196 ± 0.115 | 68.41 (54.81–85.38)c | 63.59 (50.87–79.49)c |
| Cmax (ng/mL) | 0.317 ± 0.111 | 0.342 ± 0.135 | 0.387 ± 0.172 | 84.69 (66.91–107.20) | 89.63 (70.43–114.06) |
| AUC24h (ng·h/mL) | 4.74 ± 1.83 | 4.94 ± 1.95 | 6.35 ± 2.79 | 74.71 (56.64–98.56) | 77.85 (58.65–103.34) |
SD standard deviation, LS least squares, CI confidence interval, C0h observed plasma concentration prior to the beginning of a dosing interval, ND not determined, Cmin minimum plasma concentration, Cmax maximum plasma concentration, tmax time to reach the maximum plasma concentration, AUC24h area under the plasma concentration versus time curve from time of administration to 24 h postdose, BLQ below the limit of quantification, LLOQ lower limit of quantification
aBLQ values were excluded for Cmin; second trimester, n = 14; third trimester, n = 13; and postpartum, n = 10. Statistical analyses were also performed including the BLQ values (included as 0.5 × LLOQ); the LS mean ratio (90% CI) for the second trimester versus postpartum was then 75.50 (31.35–181.80), and for the third trimester versus postpartum was 95.81 (38.46–238.64)
bData are presented as median (range)
cBLQ values were excluded for Cmin; second trimester, n = 14; third trimester, n = 13; and postpartum, n = 10. Statistical analyses were also performed including the BLQ values (included as 0.5 × LLOQ); the LS mean ratio (90% CI) for the second trimester versus postpartum was then 82.70 (33.76–202.61), and for the third trimester versus postpartum was 111.74 (43.97–283.93)