Pharmacokinetics of chlordesmethyldiazepam after single-dose oral administration in humans

  • S. R. Bareggi
  • R. Pirola
  • S. eva
  • L. Zecca
Original Papers

Summary

The pharmacokinetics of chlordemethyldiazepam — a pharmacologically very active new 1,4-benzodiazepine derivative — in healthy subjects after administration of a single oral dose of 2 mg, was studied. Peak concentrations were reached in 1.2 ± 0.2 hours. Plasma levels declined with a biphasic pattern, and the elimination phase had a half-life of 82.9 ± 14.1 hours. The concentrations of the main metabolite of chlordemethyldiazepam, lorazepam, were about 7% of those of the parent compound. In urine only conjugated lorazepam could be found its 96 hour excretion reaching about 15% of the administered dose of parent drug.

Key-words

Chlordemethyldiazepam pharmacokinetics metabolism 

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References

  1. 1.
    De Angelis L., Traversa V. and Vertua R. (1974): Structure activity relationship within the class of 1,4, benzodiazepines: presence of chlorine and central nervous system activities. Curr. Ther. Res.,16, 324–337.PubMedGoogle Scholar
  2. 2.
    Traversa U., De Angelis L. and Vertua R. (1977): On the hypnogenic and anticonvulsant activities of demethyldiazepam and chlordemethyldiazepam: time-effect relations. J. Pharm. Pharmacol.,29, 504–506.PubMedGoogle Scholar
  3. 3.
    Castellani A., Colafeiice M., Lorini M. and Perbellini D. (1979): A single blind, crossover comparison of the anxiolitic activity of chlordemethyldiazepam: analysis of single item changes. Clin. Ther.,2, 343–351.Google Scholar
  4. 4.
    Agricola A., Mazzarino M., Agricola R., Urani R. and Fresia P. (1981): A double-blind, crossover clinical trial of chlordemethyldiazepam versus lorazepam in neurotic inpatients: activity on anxiety-depression symptoms. Clin. Ther.,4, 339–408.Google Scholar
  5. 5.
    Dal Bo L., Marcucci F., Mussini E., Perbellini D., Castellani A. and Fresia P. (1980): Plasma levels of chlordesmethyldiazepam in human. Biopharm. Drug Dispos.,1, 123–126.CrossRefGoogle Scholar
  6. 6.
    Lanzoni J., Airoldi L., Marcucci F. and Mussini E. (1979): Gas chromatographic determination of chlordesmethyl diazepam and lorazepam in rats and mice. J. Chromatogr.,168, 260–265.CrossRefPubMedGoogle Scholar
  7. 7.
    Williams T.H. and Sasso G.J. (1979): Novel application of proton nuclear magnetic resonance spectroscopy in the identification of 2-chloronordiazepam in the dog. J. Med. Chem.,22, 436–440.CrossRefPubMedGoogle Scholar
  8. 8.
    De Silva J.A.F., Bekersky I. and Puglisi C.V. (1973): The determination of 7-chloro-1,3-dihydro-5-(2,chlorphenyl)-2H-1,4-benzodiazepin-2-one (RO-5-3027) and its metabolite (lorazepam) in blood and urine by electron-capture gas-liquid chromatography. J. Chrom. Sc.,11, 547–554.Google Scholar
  9. 9.
    Greenblatt D.J., Franke K. and Shader R.I. (1978): Analysis of Lorazepam and its glucuronide metabolite by electron-capture gas-liquid chromatography. Use in pharmacokinetic studies of Lorazepam. J. Chromatogr.,146, 311–320.CrossRefPubMedGoogle Scholar
  10. 10.
    Sacchi Landriani G., Guardabasso V. and Rocchetti M. (1983): NL-FIT: a microcomputer program for non-linear fitting. Comput. prog. Biomed.,16, 35–42.CrossRefGoogle Scholar
  11. 11.
    Bareggi S.R., Nielsen N.P., Leva S., Pirola R., Zecca L. and Lorini M. (1986): Age-related multiple-dose kinetics and anxiolytic effects of Delorazepam (Chlordesmethyldiazepam). Int. J. Clin. Pharm. Res.,6, 309–314.Google Scholar
  12. 12.
    Greenblatt D.J., Shader R.I., Franke K., MacLaughlin D.S., Harmatz J.S., Divoll M.D., Werner A. and Woo E. (1979): Pharmacokinetics and bioavailability of intravenous, intramuscular, and oral Lorazepam. J. Pharm. Sci.,68, 57–63.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • S. R. Bareggi
    • 1
  • R. Pirola
    • 1
  • S. eva
    • 1
  • L. Zecca
    • 1
  1. 1.Department of PharmacologyMedical school State UniversityMilanItaly

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