title: Human safety and pharmacokinetic study of intramuscular midazolam administered by autoinjector.
abstract: 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.
authors.affiliation: Reichard Consulting, LLC, Frederick, Maryland, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Reichard
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Atkinson
authors.forename: S Peter
authors.initials: SP
authors.lastname: Hong
authors.forename: Brian L
authors.initials: BL
authors.lastname: Burback
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Corwin
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Johnson
mesh_terms: D000328:Adult; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D008297:Male; D008874:Midazolam / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D012737:Sex Factors
chemical_list: D006993:Hypnotics and Sedatives; D008874:Midazolam