Table 1.
Mean (± standard deviation)* pharmacokinetic parameters and statistical results for total and unbound darunavir and total ritonavir, after administration of darunavir/ritonavir 600/100 mg twice daily (bid), during the second and third trimesters and postpartum
| Postpartum (6–12 weeks) (reference) | Second trimester of pregnancy | Third trimester of pregnancy | LSM ratio (90% CI) |
||
|---|---|---|---|---|---|
| Second trimester vs. reference | Third trimester vs. reference | ||||
| Pharmacokinetics of total darunavir | |||||
| n | 11 | 11† | 11 | 11†:11 | 11:11 |
| C0h (ng/mL) | 3 497 ± 2 922 | 2 403 ± 1 161 | 3 028 ± 1 236 | ND | ND |
| Cmin (ng/mL) | 2 711 ± 2 268 | 1 980 ± 840 | 2 498 ± 1 193 | 1.43 (0.39–5.22) | 1.86 (0.49–7.04) |
| Cmax (ng/mL) | 6 499 ± 2 411 | 4 601 ± 1 125 | 5 111 ± 1 517 | 0.72 (0.61–0.86) | 0.81 (0.69–0.96) |
| C12h (ng/mL) | 3 194 ± 1 847 | 2 268 ± 624 | 2 807 ± 1 446 | ND | ND |
| tmax (h) | 3.00 (1.00–6.00) | 3.00 (0.93–5.83) | 3.00 (2.00–11.88) | ND | ND |
| AUC12h (ng/h/mL) | 55 300 ± 27 020 | 38 950 ± 10 010 | 43 700 ± 16 400 | 0.76 (0.63–0.90) | 0.83 (0.72–0.97) |
| CL/F (L/h) | 12.79 ± 5.19 | 16.45 ± 4.65 | 15.60 ± 5.73 | ND | ND |
| Pharmacokinetics of unbound darunavir‡ | |||||
| n | 11§ | 6¶ | 7# | 6**:11†† | 7‡‡:11†† |
| C0h (ng/mL) | 592.4 ± 446.9 | 526.3 ± 281.8 | 504.2 ± 270.1 | ND | ND |
| Cmin (ng/mL) | 420.6 ± 293.1 | 413.1 ± 243.9 | 414.8 ± 243.8 | 1.10 (0.59–2.06) | 1.14 (0.59–2.20) |
| Cmax (ng/mL) | 1 173 ± 481.0 | 933.7 ± 371.8 | 923.4 ± 286.3 | 0.78 (0.52–1.18) | 0.82 (0.57–1.16) |
| C12h (ng/mL) | 464 ± 241 | 456 ± 209 | 519 ± 336 | ND | ND |
| tmax (h) | 2.03 (1.00–4.00) | 2.92 (0.93–8.83) | 3.00 (1.00–11.88) | ND | ND |
| AUC12h (ng/h/mL) | 9 178 ± 3 956 | 7 425 ± 2 999 | 7 294 ± 2 408 | 0.92 (0.66–1.30) | 0.93 (0.69–1.24) |
| CL/F (L/h) | 77.66 ± 35.46 | 91.63 ± 33.86 | 91.20 ± 32.72 | ND | ND |
| Pharmacokinetics of total ritonavir | |||||
| n | 11 | 11§§ | 11¶¶ | 11##:11 | 11***:11 |
| C0h (ng/mL) | 418.8 ± 419.4 | 241.0 ± 120.4 | 210.2 ± 63.64 | ND | ND |
| Cmin (ng/mL) | 232.5 ± 246.1 | 149.7 ± 69.92 | 137.1 ± 39.47 | 1.08 (0.31–3.81) | 1.22 (0.41–3.59) |
| Cmax (ng/mL) | 1 016 ± 881.8 | 569.8 ± 245.6 | 515.3 ± 206.4 | 0.66 (0.41–1.08) | 0.63 (0.40–0.98) |
| C12h (ng/mL) | 309 ± 224 | 177 ± 53 | 179 ± 99 | ND | ND |
| tmax (h) | 6.00 (2.02–12.08) | 4.14 (0.93–6.08) | 4.05 (1.00–9.10) | ND | ND |
| AUC12h (ng/h/mL) | 6 746 ± 6 032 | 3 929 ± 1 203 | 3 532 ± 1 130 | 0.72 (0.44–1.17) | 0.67 (0.43–1.04) |
| CL/F (L/h) | 25.98 ± 24.95 | 27.80 ± 8.754 | 31.05 ± 9.715 | ND | ND |
LSM, least squares mean; CI, confidence interval; C0h, predose plasma concentration; ND, not determined; Cmin, minimum plasma concentration; Cmax, maximum plasma concentration; C12h, plasma concentration at 12 hours; tmax, time to reach the maximum plasma concentration; AUC12h, area under the plasma concentration–time curve over 12 h; CL/F, apparent clearance.
Median (range) for tmax.
n = 10 for AUC12h.
Data for unbound darunavir were not available for all patients because of poor sample quality (protein in the filtrate) or low sample volume.
n = 10 for C0h and Cmin.
n = 10 for C0h, n = 9 for Cmin, and n = 7 for Cmax and tmax.
n = 11 for C0h, and n = 8 for Cmin, Cmax and tmax.
n = 9 for Cmin, and n = 7 for Cmax.
n = 10 for Cmin.
n = 8 for Cmin and Cmax.
n = 12 for C0h, Cmin, Cmax and tmax.
n = 10 for Cmin.
n = 12 for Cmin and Cmax.
n = 10 for Cmin.