Table 2.
Pharmacokinetic studies of epinephrine autoinjectors. Comparison of injection in the middle part of the antero-lateral (m a-l) or distal-ventral (d-v) area of the thigh
| Subject\Study | Simons et al. | Edwards et al. 2013 [10] | Duvauchelle et al. 2018 [11] | Worms et al. [12] | Turner et al. [13] | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1998 [8] | 2001 [9] | Low STMD | Middle STMD | High STMD | ||||||||
| Brand | Epipen® | Epipen® | Epipen® | Auvi-Q® | Anapen® | Anapen® | Anapen® | Epipen® | Epipen® | Epipen® | Emerade® | Emerade® |
| Needle length, mmj | 10.5 | 15 | 15 | 15 | 10.5 | 10.5 | 10.5 | 13–18 (20) | 13–18 (20) | 13–18 (20) | 23 | 23 |
| Number of pat. | 8 | 13 | 135 | 67 | 18 | 12 | 18 | 12 | 12 | 11 | 12 | 12 |
| Gender | Children | Male, adults | Male, adults | Male, adults | Male, adults | Female, adults | Male, adults | M = 6; F = 6 | M = 6; F = 6 | M = 5; F = 6 |
Adolescent M = 7; F = 5 |
Adolescent M = 7; F = 5 |
| Weight kg |
? 15–40 |
85 ± 5; 62–114 | 77.0 ± 11.5 | 77.0 ± 11.5 | 75 ± 10.5 | 78 ± 7.9 | 75 ± 10.5 | M/F 103.5/63.6 | M/F 107.7/83.3 | M/F 122.4/85.0 |
61 41.8–76.4 |
61 41.8-76.4 |
| BMI kg/m2 | – | 36.6 ± 4.6; 29–64 | 25.4 ± 2.7 | 25.4 ± 2.7 | 23.3 ± 1.9; 18–26 | 29.7 ± 1.9; 26–34 | 23.3 ± 1.9; 18–26 | M/F 32.4/21.3 | M/F 32.2/28.1 | M/F 36./31.4 | – | – |
| Age years | 4–12 | 18–35 | 33.2 ± 6.3 | 33.2 ± 6.3 | 31.5 ± 9.2 | 33.3 ± 9.1 | 31.5 ± 9.2 | M/F 36.2/46.0 | M/F 34.5/38.8 | M/F 32.8/39.0 | 15.4 | 15.4 |
| Site | ? | Thigh, m a-l | Thigh, m a-l | Thigh, m a-l | Thigh, m a-l | Thigh, d-v | Thigh, m a-l | Thigh, m a-l | Thigh, m a-l | Thigh, m a-l | Thigh m a-l | Thigh m a-l |
| Rote | i.m.a | i.m.a | i.m.a | i.m.a | i.m. | i.m.a i | i.m. | i.m.a | i.m.a | i.m.a | i.m. | i.m. |
| Dose mg | 0.3 | 0.3 | 0.3 | 0.3 | 0.3 | 0.3 | 0.3 | 0.3 | 0.3 | 0.3 | 0.3 | 0.5 |
| Plasma level analyzes hours | 3 | 3 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 3 | 3 |
| Tmax 1, minutes |
8 ± 2c 5 |
10f | 5–10g; 5i | 5–10g; 5i | 12 ± 7; 5d | 14 ± 6; 15d | 13 ± 7; 5d | 9 (3–60) | 10,5 (2–39) | 30 (9–120) | – | – |
| Tmax 2, minutes | ≈ 20e | ≈ 40f | 25–308) | 25–30h | ≈ 50d | ≈ 30d | ≈ 50d | – | – | – | – | – |
| Cmax1 pg/ml | 2136 ± 351 | 12,222 ± 3829 | 520 | 486 |
377. ± 298 275d |
440 ± 416 ≈ 250d |
353.9 ± 283 ≈260d |
M/F 400/640 |
M/F 480/520 |
M/F 420/630 |
– | – |
| Cmax2 pg/ml | 1000f | ≈ 6000f | ≈ 300h | ≈ 330h | ≈ 250d | ≈ 275d | ≈290d | – | – | – | – | – |
| No of Cmax | 1? | 2 | 2 | 2 | 2 | 2? | 2 | 2 | 2 | 2 | 2 | 2 |
| AUC0-20 h*pg/mk | – | – | – | – | 69.3 ± 54 | 55.9 ± 45 | 68.4 ± 50 | – | – | |||
| AUC0-t h*pg/ml | – | – | 466 | 536 | – | – | – | M/F 273/288 | M/F 281/209 |
M/F 263/311 |
– | – |
| AUCinf h*pg/ml | 108,000 ± 18,000 | – | 583 | 724 | 459.2 ± 129 | 677.7 ± 161 | 473.1 ± 139 | – | – | – | – | – |
aIntended localization of the bolus; cIn the s.c. group, 2/9 children and in the i.m. group, 6/8 children showed a Tmax at 5 min. [8]; d Estimated from Figure 3 in [11]; e Estimated from Figure 1 in [8]. f According to Figure 1 in [9]; g Approximately according to Table 3 in [10]; h According to Figure 2 in [10]; i s.c. in 10/12 women, i.m in 2/12 women as localized by ultrasound [10]. j The variation 5 mm for Epipen®, not known for Anapen® [11, 27]; k Worm [12]: AUC registered for 6, 15 and 30 min, but data not reported