Blood level, metabolism and excretion of [14C]-brotizolam in mice

  • W. D. Bechtel


Blood level, metabolite pattern and excretion of [14C]-brotizolam, a hypnotic drug, were studied in mice following oral administraiton. [14C]-Brotizolam was rapidly absorbed which was indicated by a Tmax of the blood level of 0.5 h. Radioactive compounds were eliminated from the blood with a half-life of 5.6 h. Total excretion of radioactivity, the renal portion of which was 22.4%, was complete after 4 days. [14C]-Brotizolam was almost completely metabolized. Using TLC, HPLC and radioactivity measurement, the main metabolite in bile, urine and plasma was found to be brotizolam hydroxylated at the methyl group. Other major metabolites were brotizolam hydroxylated at the diazepine ring and a combination of both hydroxylations. In the bile, all metabolites were conjugated. The metabolism of brotizolam in mice is similar to that in dogs, monkeys and man but not in rats.


Brotizolam blood level pharmacokinetics metabolism excretion mice 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Nicholson A.N., Stone B.M., Pascoe P.A. (1980): Studies on sleep performance with a triazolo-l,4-thieno-diazepine (Brotizolam). Br. J. Clin. Pharmacol., 10, 75–81.PubMedGoogle Scholar
  2. 2.
    Goetzke E., Findeisen P., Welbers I.B. (1983): Efficacy and tolerance: comparative studies with brotizolam and flunitrazepam. Br. J. Clin. Pharmacol., 16, 397S-402S.PubMedGoogle Scholar
  3. 3.
    Lohmann H., v. Delbrück O., Findeisen P. (1983): Comparative studies on the efficacy of brotizolam and nitrazepam: a multi-centre study. Br. J. Clin. Pharmacol., 16, 403S-406S.PubMedGoogle Scholar
  4. 4.
    Bechtel W.D., Mierau J., Richter I., Stiasni M. (1986): Blood level, distribution, excretion and metabolite partem of [14C]brotizolam in the rat, dog and rhesus monkey. Arzneim. Forsch., 36, 568–574.Google Scholar
  5. 5.
    Bechtel W.D. (1983): Pharmacokinetics and metabolism of brotizolam in animals. Br J. Clin. Pharmacol., 16, 261S-266S.PubMedGoogle Scholar
  6. 6.
    Jochemsen R., Wesselman J.G.J., Hermans J., van Boxtel C.J., Breimer D.D. (1983): Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration. Br. J. Clin. Pharmacol., 16, 285S-290S.PubMedGoogle Scholar
  7. 7.
    Bechtel W.D., van Wayjen R.G.A., van den Ende A. (1986): Blood level, excretion, and metabolite pattern of [14C]-brotizolam in humans. Arzneim. Forsch., 36, 575–578.Google Scholar
  8. 8.
    Bechtel W.D., Mierau J., Brandt K., Förster H.J., Pook K.H. (1986): Metabolic fate of [14C]brotizolam in the rat, dog, monkey and man. Arzneim. Forsch., 36, 578–586.Google Scholar
  9. 9.
    Weber K.H., Sirrenberg W., Spohn O., Daniel H. (1986): Chemistry of brotizolam and its metabolites. Arzneim. Forsch., 36,518–521.Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • W. D. Bechtel
    • 1
  1. 1.Department of BiochemistryBoehringer Ingelheim KGIngelheim am RheinFRG

Personalised recommendations