D3.289 - Pharmacokinetics of adrenaline administered via the ZiBiPen: First human trial findings

The drawbacks of single-use adrenaline auto-injectors—primarily their high cost and limited shelf-life—coupled with the critical clinical need for fast, reliable adrenaline delivery in anaphylactic emergencies, underscore the potential advantages of a reusable, reloadable auto-injector for improved emergency preparedness and patient care.  The ZiBiPen is a reusable adrenaline auto-injector that reduces costs by enabling patients to replace expired cartridges with pre-approved adrenaline. This study reports the initial pharmacokinetic findings from its first human trials.

Thirteen healthy adults (BMI 18.5–30 kg/m², weight >50 kg) consumed a normocaloric breakfast one hour before receiving a 0.3 mg intramuscular adrenaline injection via the ZiBiPen. Blood samples were collected at predetermined intervals and analyzed using liquid chromatography-tandem mass spectrometry to quantify adrenaline levels, with the resulting pharmacokinetic profile compared against published EpiPen® data.

Participants had an average age of 29 years, with no severe adverse events reported and only minor effects consistent with known adrenaline pharmacology. Adrenaline absorption exhibited a biphasic pattern, with mean Cmax values of 462.7 pg/mL, 302.2 pg/mL (Cmax1), and 419.9 pg/mL (Cmax2) at corresponding Tmax values of 24, 5, and 31 minutes, and mean concentrations of 296.1 pg/mL and 380.5 pg/mL. The ZiBiPen's AUC₀₋ₜ was 592.9 h·pg/mL, aligning with published EpiPen® AUC values (411–500 h·pg/mL), with parameters AUC, Cmax, Cmax1, Tmax, Tmax1, and Tmax2 falling within an 80–120% equivalence range to EpiPen® values, except for a slightly higher Cmax2.

The ZiBiPen demonstrated a pharmacokinetic profile comparable to the EpiPen®, supporting its safety and effectiveness for adrenaline delivery in emergency settings. Its reloadable design offers significant potential to reduce costs and enhance accessibility in anaphylaxis management.