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European Journal of Clinical Pharmacology

, Volume 35, Issue 1, pp 59–64 | Cite as

Influence of repeated administration of cimetidine on the pharmacokinetics and pharmacodynamics of adinazolam in healthy subjects

  • R. Hulhoven
  • J. P. Desager
  • S. Cox
  • C. Harvengt
Originals

Summary

Adinazolam is a new triazolobenzodiazepine bearing an alkyl-amino side chain. A cross-over double-blind placebo controlled study was carried out in 12 healthy volunteers, in order to check the possible interaction between cimetidine and adinazolam after repeated co-administration.

Cimetidine or placebo were given during 17 days. Beginning on Day 8 of each treatment, adinazolam was given in the increasing doses following sequence of doses for 3 days: 10 mg b.i.d., 20 mg b.i.d. and 20 mg t.i.d. A pharmacokinetic and pharmacodynamic study was performed on the third day at each dose. A wash-out of three weeks was included between the two treatments.

Cimetidine increased significantly the AUC values of both adinazolam and N-desmethyladinazolam, reduced the oral clearance of adinazolam, and prolonged adinazolam's half-life.

The digit symbol substitution test was significantly affected at each dose level while the manual dexterity was marginally impaired by adinazolam plus cimetidine.

Saftee-up interview and Clyde mood scale indicated an increased sedation under adinazolam plus cimetidine in four subjects.

Key words

adinazolam cimetidine pharmacokinetics pharmacodynamics healthy volunteers adverse effects 

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Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • R. Hulhoven
    • 1
  • J. P. Desager
    • 1
  • S. Cox
    • 2
  • C. Harvengt
    • 1
  1. 1.Laboratoire de PharmacothérapieUniversité Catholique de LouvainBruxellesBelgium
  2. 2.Upjohn Research CenterKalamazooUSA

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