Table 3.
Pharmacokinetic parameters at steady state (day 36) for glepaglutide and individual analytes following once-weekly dosing
| Parameter | Glepaglutide | Individual analytes | ||
|---|---|---|---|---|
| Parent | M1 | M2 | ||
| SC glepaglutide 5 mg after 6 once-weekly doses | ||||
| AUClast (h × pmol/L) | 119,000 (56.6%) [15] | 516 (87.2%) [13] | 6590 (113%) [15] | 109,000 (57.8%) [15] |
| AUCτ (h × pmol/L) | 106,000 (53.2%) [15] | 833 (47.5%) [6] | 7650 (86.7%) [15] | 96,600 (54.4%) [15] |
| Cmax (pmol/L) | 2830 (66.9%) [15] | 223 (52.4%) [15] | 371 (98.7%) [15] | 2510 (71.4%) [15] |
| tmax (h); median (min-max) | 12.0 (8.00–24.1) [15] | 0.52 (0.45–1.03) [15] | 8.00 (0.93–12.0) [15] | 24.0 (8.02–24.1) [15] |
| t1/2, z (h), mean (SD) | 228 (474) [14] | 3.8 (2.5) [6] | 17.0 (6.53) [15] | 231 (475) [14] |
| CL/F (L/h) | 1390 (47.5%) [6] | |||
| MRAUCτ | 6.82 (151%) [6] | 95.4 (62.3%) [6] | ||
| RAAUC | 1.64 (51.0%) [15] | 0.649 (67.7%) [3] | 0.932 (53.9%) [13] | 1.75 (54.5%) [15] |
| t1/2, eff (h); estimated mean (95% CI) | 123.7 (73.3–184.9) [15] | |||
| SC glepaglutide 10 mg after 6 once-weekly doses | ||||
| AUClast (h × pmol/L) | 281000 (86.8%) [14] | 1040 (79.3%) [14] | 14300 (117%) [14] | 259000 (90.1%) [14] |
| AUCτ (h × pmol/L) | 232000 (94.7%) [14] | 1450 (74.6%) [10] | 15200 (108%) [14] | 211000 (99.7%) [14] |
| Cmax (pmol/L) | 5940 (97.1%) [14] | 432 (34.2%) [14] | 716 (102%) [14] | 5320 (106%) [14] |
| tmax (h), median (min–max) | 12.1 (4.00–36.0) [14] | 0.53 (0.47–2.05) [14] | 8.00 (4.00–12.0) [14] | 18.1 (4.00–36.0) [14] |
| t1/2, z (h); mean (SD) | 254 (198) [8] | 2.8 (2.1) [10] | 37.7 (44.2) [14] | 255 (251) [9] |
| CL/F (L/h) | 1600 (74.6%) [10] | |||
| MRAUCτ | 9.93 (134%) [10] | 153 (61.0%) [10] | ||
| RAAUC | 1.37 (53.3%) [14] | 0.695 (42.7%) [9] | 0.829 (68.5%) [14] | 1.43 (57.0%) [14] |
| t1/2, eff (h), estimated mean (95% CI) | 88.3 (30.6–146.3) [14] | |||
Geometric mean (CV%) is presented unless otherwise specified. Numbers in square brackets denote the number of subjects included in the analysis
AUClast area under the plasma concentration–time curve from time zero to the time of the last measurable concentration, AUCτ area under the plasma concentration–time curve over a dosing interval, CI confidence interval, CL/F apparent total plasma clearance, Cmax maximum observed plasma concentration, CV coefficient of variation, h hours, max maximum, min minimum, MRAUCτ metabolite: parent ratio based on AUCτ, RAAUC accumulation index based on the area under the curve over the dosing interval, SD standard deviation, t1/2, eff effective half-life, t1/2, z apparent plasma terminal elimination half-life, tmax time of the maximum observed plasma concentration