European Journal of Clinical Pharmacology

, Volume 19, Issue 4, pp 271–278

The pharmacokinetics of midazolam in man

  • M. T. Smith
  • M. J. Eadie
  • T. O'Rourke Brophy
Originals

DOI: 10.1007/BF00562804

Cite this article as:
Smith, M.T., Eadie, M.J. & Brophy, T.O. Eur J Clin Pharmacol (1981) 19: 271. doi:10.1007/BF00562804

Summary

Midazolam, a new water-soluble benzodiazepine, was administered as: i) 5 mg intravenously, ii) a 10-mg oral solution and iii) a 10-mg oral tablet, to six volunteers whose informed consent had been obtained. Midazolam plasma concentrations were measured using an electron-capture gas-liquid chromatographic assay. After 5-mg intravenous midazolam, subjects fell asleep within 1–2 min and continued to sleep for an average of 1.33 h. After oral midazolam intake (solution or tablets), drowsiness appeared after a average of 0.38 h (range 0.25–0.55 h) and sleep continued for an average of 1.17 h. The time to reach peak plasma midazolam concentration after the 10-mg solution dose (0.37±0.45 h) did not differe significantly (‘t’=2.04, df=10,p>0.05) from the time to reach peak plasma midazolam level after the 10-mg tablet dose (0.74±0.45 h). The terminal half-life, (t1/2), of midazolam in plasma was 1.77±0.83 h and there was no significant difference between the mean terminal half-life values obtained for the three midazolam formulations. The mean total clearance (Cl), of midazolam after 5-mg intravenous administration was 0.383±0.094 l·kg−1·h−1. The first pass effect, F, determined experimentally (0.36±0.09) indicated the substantial first pass metabolism of midazolam. The percentage of the midazolam dose excreted unchanged in urine in four subjects during the 0-8-h urine collection interval was very small (0.011%–0.028%).

Key words

midazolam benzodiazepine pharmacokinetics gas-liquid chromatography first-pass metabolism 

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • M. T. Smith
    • 1
  • M. J. Eadie
    • 1
  • T. O'Rourke Brophy
    • 2
  1. 1.Department of MedicineUniversity of Queensland, Royal Brisbane HospitalBrisbaneAustralia
  2. 2.Department of SurgeryUniversity of Queensland, Royal Brisbane HospitalBrisbaneAustralia