Relative Bioavailability Study of Midazolam Intramuscularly Administered with the Needle-Free Auto-Injector ZENEO® in Healthy Adults

Autor: Olivier Lacombe, Yannick Pletan, Jean-Marie Grouin, Aislinn Brennan, Olivier Giré
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Neurology and Therapy, Vol 13, Iss 4, Pp 1155-1172 (2024)
Druh dokumentu: article
ISSN: 2193-8253
2193-6536
DOI: 10.1007/s40120-024-00627-4
Popis: Abstract Introduction Intramuscular (IM) midazolam is indicated for the treatment of status epilepticus. Administration must be efficient to rapidly terminate prolonged seizures and prevent complications. The objective of this study was to compare, in terms of relative bioavailability and bioequivalence, IM midazolam injection by needle-free auto-injector, in different settings, to IM midazolam injection by a conventional syringe and needle. Methods In this open-label, randomized, four-period crossover study, healthy adults received single doses of midazolam (10 mg) under fasting conditions. The reference treatment (conventional syringe) was administered once, on bare skin in the thigh. The tested treatment (the needle-free auto-injector ZENEO®) was administered three times: on bare skin in the thigh, on bare skin in the ventrogluteal area, and through clothing in the thigh. Repeated plasma samples were collected to obtain 36-h pharmacokinetic (PK) profiles. Primary PK parameters were area under the plasma concentration–time curve, from time zero to the last measurable time point (AUC0−t) and from time zero to infinity (AUC0–∞), and the maximum observed plasma concentration (C max). Results Forty adults were enrolled and included in the PK analysis set. In all comparisons, the 90% confidence interval (CI) of the least-squares geometric mean ratios for AUC0−t and AUC0−∞ were within the bioequivalence range of 80–125%, with low intra-individual coefficients of variation (
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