Table 2.
Pharmacokinetic similarity analysis for the somatropin data
| Formulation R | Formulation T1 | Formulation T2 | T1/R | T2/R | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
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| Dataset | PK parameter | Method | Geometric mean | CV (%) | Geometric mean | CV (%) | Geometric mean | CV (%) | Ratio (%) | 90% CI (%) | Ratio (%) | 90% CI (%) |
| C | AUC0-∞ (h.ng/mL) | NLMEM | 579.1 | 25.0 | 574 | 25.0 | 550.1 | 25.0 | 99.1 | [95.0; 103.4] | 95.0 | [91.0; 99.1] |
| NCA | 574.5 | 21.6 | 565.7 | 26.2 | 544 | 24.9 | 98.5 | [94.1;103.1] | 94.6 | [90.4; 99.1] | ||
| Cmax (ng/mL) | NLMEM | 69.5 | 38.1 | 66.0 | 38.1 | 63.5 | 38.1 | 95.0 | [87.5; 103.0] | 91.4 | [84.5; 98.8] | |
| NCA | 73.7 | 34.5 | 70.0 | 31.9 | 68.6 | 37.9 | 95.3 | [87.8;103. 3] | 93.1 | [85.9; 101.0] | ||
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| OD | AUC0-∞ (h.ng/mL) | NLMEM | 559.2 | 25.9 | 550.2 | 25.9 | 524.1 | 25.9 | 98.4 | [94.1; 102.9] | 93.7 | [89.6; 98.0] |
| NCA | 491.3 | 23.2 | 491.6 | 29.3 | 464.2 | 26.4 | 100.1 | [95.6; 104.9] | 94.4 | [90.1; 98.9] | ||
| Cmax (ng/mL) | NLMEM | 68.6 | 38.8 | 63.7 | 38.8 | 60.7 | 38.8 | 92.9 | [85.2; 101.3] | 88.5 | [81.4; 96.2] | |
| NCA | 59.7 | 42.2 | 55.1 | 45.3 | 54.0 | 47.8 | 92.6 | [83.4; 102.8] | 90.4 | [81.4; 100.4] | ||
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| ED | AUC0-∞ (h.ng/mL) | NLMEM | 586.4 | 23.2 | 597.0 | 23.2 | 565.1 | 23.2 | 101.8 | [97.8; 106] | 96.4 | [92.5; 100.4] |
| NCA | 566.4 | 21.6 | 570 | 26 | 541.9 | 25.6 | 100.7 | [96.1; 105.6] | 95.6 | [91.2; 100.2] | ||
| Cmax (ng/mL) | NLMEM | 70.8 | 38.2 | 68.1 | 38.2 | 65.2 | 38.2 | 96.2 | [88.8; 104.1] | 92.0 | [85.0; 99.7] | |
| NCA | 72.4 | 34.3 | 68.6 | 32.4 | 67.5 | 37.0 | 95.0 | [87.5; 103.2] | 93.3 | [86.0; 101.3] | ||
AUC0-∞, area under the curve between the time of dose and infinity; C, complete dataset; Cmax, maximal concentration; CV, coefficient of variation; CI, confidence interval; ED, empirical design dataset; NCA, non-compartmental analysis; NLMEM, nonlinear mixed effects model; OD, optimized design dataset; PK, pharmacokinetic.