title: Comparative absorption kinetics of intramuscular midazolam and diazepam.
abstract: OBJECTIVE
  This study investigates the rate and extent of absorption following intramuscular injection of midazolam and diazepam.
  
  
  METHODS
  Four healthy male volunteers were recruited in this randomized three-way cross-over study. On one occasion each subject received simultaneous im injections of 5 mg midazolam and 10 mg diazepam in separate deltoid muscles. On two other separate occasions each subject received an iv infusion of 7.5 mg midazolam and 30 mg diazepam over five minutes. Frequent arterial blood samples were collected for up to two hours and venous blood samples were collected for up to 24 hours for midazolam and ten days for diazepam. A gas chromatography assay was used to determine the plasma concentrations of midazolam and diazepam. The im absorption profiles were estimated using constrained least-squares deconvolution.
  
  
  RESULTS
  There were substantial intersubject variabilities in the estimated pharmacokinetic parameters (volume and clearances) of intravenous midazolam and diazepam. The mean (+/-sd) time to peak plasma concentration (Cmax) was shorter for im midazolam (17.5 +/- 6.5 min) relative to diazepam (33.8 +/- 7.5 min). The mean (+sd) time to peak absorption rate was also shorter for midazolam (9 +/- 2 vs 13.8 +/- 7.5 min). The peak rate of absorption was identical (0.18 mg. min-1) and bioavailability was 1.0 for both drugs.
  
  
  CONCLUSIONS
  We conclude that midazolam has more rapid absorption than diazepam following im administration.
authors.affiliation: Department of Anaesthesia, Dalhousie University, Halifax, Nova Scotia, Canada. hungorla@ac.dal.ca
authors.forename: O R
authors.initials: OR
authors.lastname: Hung
authors.forename: J B
authors.initials: JB
authors.lastname: Dyck
authors.forename: J
authors.initials: J
authors.lastname: Varvel
authors.forename: S L
authors.initials: SL
authors.lastname: Shafer
authors.forename: D R
authors.initials: DR
authors.lastname: Stanski
mesh_terms: D000042:Absorption; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D003975:Diazepam / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged
chemical_list: D006993:Hypnotics and Sedatives; D003975:Diazepam; D008874:Midazolam