Epinephrine delivery via EpiPen® Auto-Injector or manual syringe across participants with a wide range of skin-to-muscle distances
Abstract Background Intramuscular (IM) injection of epinephrine (adrenaline) at the mid-anterolateral (AL) thigh is the international standard therapy for acute anaphylaxis. Concerns exist regarding implications of epinephrine auto-injector needles not penetrating the muscle in patients with greater...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-06-01
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| Series: | Clinical and Translational Allergy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13601-020-00326-x |
| _version_ | 1819018304977633280 |
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| author | Margitta Worm DucTung Nguyen Russ Rackley Antonella Muraro George Du Toit Tracey Lawrence Hong Li Kurt Brumbaugh Magnus Wickman |
| author_facet | Margitta Worm DucTung Nguyen Russ Rackley Antonella Muraro George Du Toit Tracey Lawrence Hong Li Kurt Brumbaugh Magnus Wickman |
| author_sort | Margitta Worm |
| collection | DOAJ |
| description | Abstract Background Intramuscular (IM) injection of epinephrine (adrenaline) at the mid-anterolateral (AL) thigh is the international standard therapy for acute anaphylaxis. Concerns exist regarding implications of epinephrine auto-injector needles not penetrating the muscle in patients with greater skin-to-muscle-distances (STMD). Methods This open-label, randomized, crossover study investigated pharmacokinetics and pharmacodynamics following injection of epinephrine in healthy volunteers. Individuals were stratified by maximally compressed STMD (low, < 15 mm; moderate, 15–20 mm; high, > 20 mm). Participants received epinephrine injections via EpiPen® Auto-Injector (EpiPen; 0.3 mg/0.3 mL) or IM syringe (0.3 mg/0.3 mL) at mid-AL thigh or received saline by IM syringe in a randomized order. Eligible participants received a fourth treatment (EpiPen [0.3 mg/0.3 mL] at distal-AL thigh). Model-independent pharmacokinetic parameters and pharmacodynamics were assessed. Results There were numerical trends toward higher peak epinephrine concentrations (0.52 vs 0.35 ng/mL; geometric mean ratio, 1.40; 90% CI 117.6–164.6%) and more rapid exposure (time to peak concentration, 20 vs 50 min) for EpiPen vs IM syringe at mid-AL thigh across STMD groups. Absorption was faster over the first 30 min for EpiPen vs IM syringe (partial area under curve [AUC] over first 30 min: geometric mean ratio, 2.13; 90% CI 159.0–285.0%). Overall exposure based on AUC to the last measurable concentration was similar for EpiPen vs IM syringe (geometric mean ratio, 1.13; 90% CI 98.8–129.8%). Epinephrine pharmacokinetics after EpiPen injection were similar across STMD groups. Treatments were well tolerated. Conclusions Epinephrine delivery via EpiPen resulted in greater early systemic exposure to epinephrine vs IM syringe as assessed by epinephrine plasma levels. Delivery via EpiPen was consistent across participants with a wide range of STMD, even when the needle may not have penetrated the muscle. Trial registrationsThis trial was registered with the German Clinical Trials Register (DRKS-ID: DRKS00011263; secondary ID, EudraCT 2016-000104-29) on 23 March 2017. |
| first_indexed | 2024-12-21T03:17:18Z |
| format | Article |
| id | doaj.art-706b9bee34a4432baf1fedace4238688 |
| institution | Directory Open Access Journal |
| issn | 2045-7022 |
| language | English |
| last_indexed | 2024-12-21T03:17:18Z |
| publishDate | 2020-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Allergy |
| spelling | doaj.art-706b9bee34a4432baf1fedace42386882022-12-21T19:17:49ZengWileyClinical and Translational Allergy2045-70222020-06-0110111310.1186/s13601-020-00326-xEpinephrine delivery via EpiPen® Auto-Injector or manual syringe across participants with a wide range of skin-to-muscle distancesMargitta Worm0DucTung Nguyen1Russ Rackley2Antonella Muraro3George Du Toit4Tracey Lawrence5Hong Li6Kurt Brumbaugh7Magnus Wickman8Division of Allergy and Immunology, Department of Dermatology and Allergy, Charité UniversitätsmedizinMeda Pharma GmbH & Co KGMylan IncFood Allergy Referral Centre, Department of Woman and Child Health, Padua University HospitalChildren’s Allergy Service, Evelina London, Guy’s and St Thomas’ HospitalMylan IncMylan IncMylan IncCentre for Clinical Research Sörmland, Uppsala UniversityAbstract Background Intramuscular (IM) injection of epinephrine (adrenaline) at the mid-anterolateral (AL) thigh is the international standard therapy for acute anaphylaxis. Concerns exist regarding implications of epinephrine auto-injector needles not penetrating the muscle in patients with greater skin-to-muscle-distances (STMD). Methods This open-label, randomized, crossover study investigated pharmacokinetics and pharmacodynamics following injection of epinephrine in healthy volunteers. Individuals were stratified by maximally compressed STMD (low, < 15 mm; moderate, 15–20 mm; high, > 20 mm). Participants received epinephrine injections via EpiPen® Auto-Injector (EpiPen; 0.3 mg/0.3 mL) or IM syringe (0.3 mg/0.3 mL) at mid-AL thigh or received saline by IM syringe in a randomized order. Eligible participants received a fourth treatment (EpiPen [0.3 mg/0.3 mL] at distal-AL thigh). Model-independent pharmacokinetic parameters and pharmacodynamics were assessed. Results There were numerical trends toward higher peak epinephrine concentrations (0.52 vs 0.35 ng/mL; geometric mean ratio, 1.40; 90% CI 117.6–164.6%) and more rapid exposure (time to peak concentration, 20 vs 50 min) for EpiPen vs IM syringe at mid-AL thigh across STMD groups. Absorption was faster over the first 30 min for EpiPen vs IM syringe (partial area under curve [AUC] over first 30 min: geometric mean ratio, 2.13; 90% CI 159.0–285.0%). Overall exposure based on AUC to the last measurable concentration was similar for EpiPen vs IM syringe (geometric mean ratio, 1.13; 90% CI 98.8–129.8%). Epinephrine pharmacokinetics after EpiPen injection were similar across STMD groups. Treatments were well tolerated. Conclusions Epinephrine delivery via EpiPen resulted in greater early systemic exposure to epinephrine vs IM syringe as assessed by epinephrine plasma levels. Delivery via EpiPen was consistent across participants with a wide range of STMD, even when the needle may not have penetrated the muscle. Trial registrationsThis trial was registered with the German Clinical Trials Register (DRKS-ID: DRKS00011263; secondary ID, EudraCT 2016-000104-29) on 23 March 2017.http://link.springer.com/article/10.1186/s13601-020-00326-xEpinephrineAdrenalineAuto-injectorsObesityBody mass indexIntramuscular injections |
| spellingShingle | Margitta Worm DucTung Nguyen Russ Rackley Antonella Muraro George Du Toit Tracey Lawrence Hong Li Kurt Brumbaugh Magnus Wickman Epinephrine delivery via EpiPen® Auto-Injector or manual syringe across participants with a wide range of skin-to-muscle distances Clinical and Translational Allergy Epinephrine Adrenaline Auto-injectors Obesity Body mass index Intramuscular injections |
| title | Epinephrine delivery via EpiPen® Auto-Injector or manual syringe across participants with a wide range of skin-to-muscle distances |
| title_full | Epinephrine delivery via EpiPen® Auto-Injector or manual syringe across participants with a wide range of skin-to-muscle distances |
| title_fullStr | Epinephrine delivery via EpiPen® Auto-Injector or manual syringe across participants with a wide range of skin-to-muscle distances |
| title_full_unstemmed | Epinephrine delivery via EpiPen® Auto-Injector or manual syringe across participants with a wide range of skin-to-muscle distances |
| title_short | Epinephrine delivery via EpiPen® Auto-Injector or manual syringe across participants with a wide range of skin-to-muscle distances |
| title_sort | epinephrine delivery via epipen r auto injector or manual syringe across participants with a wide range of skin to muscle distances |
| topic | Epinephrine Adrenaline Auto-injectors Obesity Body mass index Intramuscular injections |
| url | http://link.springer.com/article/10.1186/s13601-020-00326-x |
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