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Human Safety and Pharmacokinetic Study of Intramuscular Midazolam Administered by Autoinjector
Author(s) -
Reichard Douglas W.,
Atkinson Andrew J.,
Hong S. Peter,
Burback Brian L.,
Corwin Michael J.,
Johnson Jerry D.
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009358083
Subject(s) - midazolam , pharmacokinetics , medicine , adverse effect , anesthesia , pharmacology , sedation
Midazolam in an autoinjector was evaluated in an open‐label dose escalation study involving 39 healthy participants. Safety and pharmacokinetic parameters were determined for doses ranging from 5 to 30 mg. No serious adverse events were noted during the study. Two participants (30 mg) experienced changes in their electrocardiogram (trigeminy and prolongation of QRS complex) that met the criteria for dose‐limiting adverse events. No significant respiratory depression was noted during the study. The midazolam doses studied exhibited a median t max of 0.5 hours with a geometric mean terminal elimination half‐life value of 4.1 hours (range, 2.9–4.5 hours). The extent of systemic exposure, assessed by area under the curve (AUC) and maximum concentration (C max ), tended to increase proportionally with increasing doses from 5 to 30 mg; however, for the male 30‐mg group, there was evidence of a larger than proportional increase in AUC.