European Journal of Clinical Pharmacology

, Volume 21, Issue 2, pp 161–163 | Cite as

Clearance of diazepam can be impaired by its major metabolite desmethyldiazepam

  • U. Klotz
  • I. Reimann
Short Communication

Summary

The pharmacokinetics of a single intravenous dose of diazepam 0.1 mg/kg was studied in 6 healthy volunteers, in random order under controlled conditions and following pretreatment with its major metabolite, desmethyldiazepam (20 mg/day) for one week. In the two subjects with the highest plasma concentration of desmethyldiazepam (990 and 1100 ng/ml, respectively), total plasma clearance (Cl) of diazepam was reduced after desmethyldiazepam, by 31% and 54%, respectively. In three individuals there was a moderate decrease of 14% to 21%, and no effect was seen in one volunteer. Cl was significantly reduced (11.5±1.8 vs. 9.1±3.3 ml/min;p=0.015) and elimination half-life tended to be prolonged (38.5±10.4 vs. 65.8±67.1 h;p=0.15). It is concluded that high concentrations of desmethyldiazepam can influence the elimination of its parent drug diazepam by product inhibition.

Key words

diazepam desmethyldiazepam product inhibition pharmacokinetics 

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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • U. Klotz
    • 1
  • I. Reimann
    • 1
  1. 1.Dr. Margarete Fischer Bosch Institut für Klinische PharmakologieStuttgartGermany

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