Table 1.
Pharmacokinetic Parameters by Treatment at Day 28 (Per-Protocol Population)
| Analyte | PK parametera | Group 1: IPE 2 g/day 1 × 1,000 mg BID (n = 10) | Group 2: IPE 4 g/day 2 × 1,000 mg BID (n = 9) | Group 3: IPE 2 g/day 2 × 1,000 mg QD (n = 12) | Group 4: IPE 2 g/day 2 × 500 mg BID (n = 12) |
|---|---|---|---|---|---|
| Total EPA in plasma | Baseline (µg/mL) | 7.9 (7.0) | 19.3 (16.1) | 19.2 (17.5) | 14.7 (16.6) |
| Cmax (µg/mL) | 154.9 (49.4) | 347.2 (112.5) | 232.8 (127.6) | 210.5 (93.1) | |
| AUC0–24 hours (µg•h/mL) | 2,907 (1,160) | 6,519 (1,963) | 2,65.9 (1,136) | 3,233 (1,104) | |
| Cmin (µg/mL) | 101.0 (50.4) | 211.9 (68.2) | 75.1 (40.5) | 104.2 (42.4) | |
| Tmax (hour) | 5 (5, 8) | 5 (3, 8) | 5 (3, 12) | 6 (5, 8) | |
| T1/2 (hour) | 75.1 (46.5) | 89.3 (42.0) | 69.7 (60.9) | 83.5 (38.8) | |
| CL/F (mL/h) | 776.4 (256.9) | 683.7 (280.6) | 867.7 (328.8) | 684.5 (248.3) | |
| Vz/F (L) | 79.8 (62.6) | 88.4 (55.2) | 79.3 (71.5) | 79.3 (35.3) | |
| Total EPA in RBCb | Baseline (µg/mL) | 5.7 (4.3) | 12.1 (15.7) | 8.2 (7.1) | 6.7 (10.4) |
| Cmax (µg/mL) | 42.3 (14.0) | 76.7 (25.2) | 31.0 (11.1) | 37.6 (15.7) | |
| AUC0–24 hours (µg•h/mL) | 801.5 (268.5) | 1,472 (469.5) | 557.6 (239.7) | 573.9 (336.4) | |
| Cmin (µg/mL) | 31.2 (12.2) | 64.1 (21.8) | 20.7 (8.6) | 26.3 (17.7) | |
| Tmax (hour) | 12 (1, 72) | 8 (1, 12) | 10 (6, 48) | 24 (0, 120) | |
| T1/2 (hour) | 683.8 (NC) | 371.4 (311.5) | 303.2 (NC) | 314.4 (194.5) | |
| Unesterified EPA in plasma | Baseline (µg/mL) | 0.13 (0.12) | 0.08 (0.05) | 0.09 (0.06) | 0.10 (0.13) |
| Cmax (µg/mL) | 0.66 (0.34) | 1.4 (0.41) | 1.4 (0.49) | 0.70 (0.24) | |
| AUC0–24 hours (µg•h/mL) | 6.9 (3.1) | 18.4 (4.6) | 9.0 (2.5) | 7.5 (2.6) | |
| Cmin (µg/mL) | 0.41 (0.28) | 1.06 (0.56) | 0.36 (0.22) | 0.44 (0.24) | |
| Tmax (hour) | 5 (0, 48) | 5 (0, 24) | 5 (3, 8) | 3 (0, 24) | |
| T1/2 (hour) | 80.8 (37.5) | 97.2 (36.5) | 136.3 (80.8) | NC | |
| CL/F (mL/h) | 364,513 (214,003) | 234,329 (81,639) | 241,855 (82,203) | 326,622 (207,574) | |
| Vz/F (L) | 33,164 (8,068) | 28,200 (10,929) | 40,873 (19,580) | NC | |
AUC0–24 hours, area under the plasma concentration versus time curve from time zero to 24 hours; BID, twice daily; CL/F, apparent total plasma clearance after an oral dose; Cmax, maximum observed concentration; Cmin, minimum observed plasma concentration; EPA, eicosapentaenoic acid; IPE, icosapent ethyl; NC, not calculated due to large variability and therefore small number of subjects for whom values could be calculated; PK, pharmacokinetic; QD, once daily; RBCs, red blood cells; SD, standard deviation; T½, elimination half-life; Tmax, time of observed Cmax; Vz/F, apparent volume of distribution after an oral dose.
Mean (SD) displayed for all PK parameters except Tmax, which is displayed as median (min, max); data based on Day 28 values except for baseline.
Packed RBCs.