Dose‐Finding and Pharmacokinetic Study of Intramuscular Midazolam

Michael J. Avram*, Robert J. Fragen, Nancy J.Caldwell CRNA

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Ten healthy male volunteers received intramuscular (IM) doses of 0.050, 0.075, and 0.100 mg/kg midazolam hydrochloride or its vehicle (placebo) in a double‐blind manner until a dose producing adequate preanesthetic sedation was administered. Level of sedation, degree of impairment of psychomotor function, existence of antegrade amnesia, and incidence of side effects were evaluated after each dose. An adequate level of sedation (awake/drowsy or asleep/easily responds to verbal command for at least one hour after drug administration) was produced, beginning shortly after drug administration, in eight of the volunteers by 0.075 mg/kg; the dose producing the same effect (the optimal dose) was 0.050 mg/kg for the oldest volunteer, and the other volunteer required 0.100 mg/kg. Sedation lasted no more than four hours after administration of the optimal dose. The optimal dose in each volunteer produced an impairment of psychomotor function that lasted no more than six hours and antegrade amnesia that lasted no more than two hours. Mild erythema at the injection site occurred infrequently. The pharmacokinetic variables describing the absorption and disposition of midazolam were determined in five of the volunteers. Pharmacokinetic studies indicated that midazolam hydrochloride is absorbed rapidly from IM injection sites; this is consistent with the observation of a rapid onset of sedation. The relatively high elimination clearance of midazolam after IM administration is similar to that reported after intravenous administration. The results of this study suggest that midazolam hydrochloride 0.075 mg/kg IM provides sedation and amnesia that is satisfactory for preanesthetic medication but does not last too long into the recovery period. 1987 American College of Clinical Pharmacology

Original languageEnglish (US)
Pages (from-to)314-317
Number of pages4
JournalThe Journal of Clinical Pharmacology
Issue number4
StatePublished - Apr 1987

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology


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