Pharmacokinetic parameters for glecaprevir, pibrentasvir, and probe substrates in each study
The Cmax, AUC, and C24 values are presented as the geometric mean (mean ± S.D.); the Tmax values are presented as the median (minimum to maximum); and the t1/2 values are presented as the harmonic mean (pseudo S.D.).
| Analyte | Administered Alone | Coadministered | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Cmax | Tmax | AUC | t1/2 | C0–24 | Cmax | Tmax | AUC | t1/2 | C0–24 | |
| ng/ml | h | ng∙h/ml | h | h | ng/ml | h | ng∙h/ml | h | h | |
| Digoxin study (N = 12) | ||||||||||
| Digoxin | 1.98 (2.06 ± 0.54) | 1.5 (0.5–2.0) | 33.4 (34.0 ± 6.9)aa | 37.0 (4.4) | — | 3.41 (3.51 ± 0.87) | 1.0 (0.5–1.0) | 49.4 (50.3 ± 10.4)a | 42.4 (5.5) | — |
| Glecaprevir | 2540 (3520 ± 2510) | 3.0 (2.0–5.0) | 8980 (11,500 ± 7600)bb | — | 5.95 (6.64 ± 3.14) | 2790 (3890 ± 3380) | 3.0 (2.0–4.0) | 9380 (12,100 ± 9600)b | — | 5.60 (6.23 ± 2.79) |
| Pibrentasvir | 208 (226 ± 96) | 4.0 (3.0–6.0) | 1730 (1880 ± 760)b | — | 23.9 (26.5 ± 11.8) | 242 (269 ± 128) | 4.5 (3.0–5.0) | 1860 (2030 ± 860)b | — | 24.1 (26.9 ± 12.5) |
| Dabigatran Etexilate study (N = 11) | ||||||||||
| Dabigatran | 181 (184 ± 38) | 4.0 (2.0–5.0) | 1540 (1580 ± 420)a | 9.9 (1.5) | — | 370 (378 ± 90) | 4.0 (3.0–5.0) | 3670 (3820 ± 1240)a | 12.4 (3.9) | — |
| Glecaprevir | 672 (838 ± 821) | 4.0 (2.0–5.0) | 2760 (3480 ± 3490)b | — | 4.62 (6.02 ± 5.15) | 549 (660 ± 492) | 4.0 (2.0–5.0) | 2200 (2740 ± 2360)b | — | 4.81 (6.72 ± 6.83) |
| Pibrentasvir | 273 (283 ± 79) | 5.0 (3.0–6.0) | 2060 (2170 ± 737)b | — | 30.7 (32.5 ± 12.3) | 236 (248 ± 90) | 5.0 (4.0–6.0) | 1880 (2030 ± 950)b | — | 29.1 (32.3 ± 17.6) |
| Pravastatin study (N = 12) | ||||||||||
| Pravastatin | 20.4 (23.0 ± 12.7) | 1.0 (1.0–2.0) | 48.6 (53.0 ± 25.8)b | — | — | 45.6 (47.8 ± 15.1) | 1.5 (1.0–4.0) | 111 (115 ± 33)b | — | — |
| Glecaprevir | 1790 (2190 ± 1380) | 3.0 (2.0–5.0) | 5870 (6890 ± 4510)b | — | 3.75 (4.98 ± 4.77) | 2850 (3410 ± 1980) | 3.0 (2.0–5.0) | 8480 (10,100 ± 6800)b | — | 4.55 (6.41 ± 7.33) |
| Pibrentasvir | 160 (168 ± 54) | 4.5 (2.0–5.0) | 906 (977 ± 385)b | — | 8.34 (9.45 ± 4.86) | 199 (205 ± 52) | 4.0 (3.0–5.0) | 1120 (1180 ± 390)b | — | 10.6 (11.8 ± 45.8) |
| Rosuvastatin Study (N = 11) | ||||||||||
| Rosuvastatin | 1.89 (2.13 ± 1.14) | 5.0 (1.0–5.0) | 17.2 (18.8 ± 8.4)b | — | 0.37 (0.40 ± .15) | 10.6 (12.2 ± 6.2) | 2.0 (2.0–4.0) | 37.0 (41.4 ± 19.2)b | — | 0.26 (0.25 ± 0.12) |
| Glecaprevir | 1860 (2270 ± 1620) | 3.0 (3.0–5.0) | 6070 (7630 ± 5520)b | — | 2.94 (3.96 ± 3.26) | 2320 (2750 ± 1580) | 4.0 (3.0–5.0) | 7340 (8630 ± 4700)b | — | 3.34 (3.88 ± 2.25) |
| Pibrentasvir | 169 (176 ± 46) | 5.0 (3.0–5.0) | 1040 (1080 ± 270)b | — | 8.93 (9.41 ± 2.93) | 208 (213 ± 46) | 5.0 (3.0–5.0) | 1250 (1290 ± 340)b | — | 12.3 (12.9 ± 4.4) |
| Sofosbuvir study (N = 16)c | ||||||||||
| Sofosbuvir | 1050 (1230 ± 640) | 1.0 (1.0–2.0) | 1410 (1540 ± 680)b | — | — | 1750 (1860 ± 650) | 1.0 (0.5–2.0) | 3170 (3290 ± 940)b | — | — |
| GS-331007 | 1470 (1590 ± 740) | 3.0 (2.0–4.0) | 12,900 (13,500 ± 4100) | — | 237 (244 ± 62) | 1260 (1320 ± 410) | 2.5 (2.0–4.0) | 15,600 (16,200 ± 4600) | — | 438 (457 ± 138) |
| Glecaprevir | 3300 (3810 ± 2120) | 3.0 (2.0–4.0) | 10,600 (13,800 ± 11,500)b | — | 4.65 (6.07 ± 4.78) | 3230 (4010 ± 3030) | 3.0 (2.0–5.0) | 10,500 (15,100 ± 14,900)b | — | 5.16 (8.23 ± 8.38) |
| Pibrentasvir | 238 (263 ± 131) | 4.0 (3.0–5.0) | 1790 (2010 ± 1090)b | — | 24.3 (27.3 ± 15.1) | 235 (270 ± 162) | 3.5 (3.0–5.0) | 1860 (2190 ± 1430)b | — | 28.1 (34.7 ± 25.3) |
AUC0–inf, AUC from time 0 to infinity; C24, plasma trough concentration 24 h after dosing; t1/2, terminal elimination half-life; Tmax, time to Cmax; —, not applicable.
↵a AUC0–inf.
↵b AUC0–24.
↵c Pharmacokinetic parameters reported for N = 8 subjects in cohort 2 (sofosbuvir and GS-331007) or N = 8 subjects in cohort 1 (glecaprevir and pibrentasvir pharmacokinetic parameters).