European Journal of Clinical Pharmacology

, Volume 19, Issue 4, pp 271–278 | Cite as

The pharmacokinetics of midazolam in man

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

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 

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References

  1. Archer GA, Sternbach LH (1968) The chemistry of benzodiazepines. Chem Rev 68: 747–784Google Scholar
  2. Gibaldi M, Perrier D (1975) In: Pharmacokinetics, vol. 1. J. Swarbrick (ed) Drugs and the pharmaceutical sciences. Marcel Dekker, New York, pp 293–296Google Scholar
  3. Puglisi CV, Meyer JC, D'Arconte L, Brooks MA, de Silva JAF (1978) Determination of water soluble imidazo-1,4-benzodiazepines in blood by electroncapture gas-liquid chromatography and in urine by differential pulse polarography. J Chromatogr 145: 81–96Google Scholar
  4. Reeves JG, Corssen G, Holcomb C (1978) Comparison of two benzodiazepines for anaesthesia induction: midazolam and diazepam. Can Anaesth Soc J 25: 211–214Google Scholar
  5. Sedman AJ, Wagner JG (1976) CSTRIP, a fortran IV computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci 65: 1006Google Scholar

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

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