Effect of cirrhosis and renal failure on the kinetics of clotiazepam.

The kinetics of a single 5-mg oral dose of the thienodiazepine clotiazepam was evaluated in a series of patients with biopsy-proven cirrhosis, and in patients with renal insufficiency requiring maintenance hemodialysis, compared to healthy matched controls. Clotiazepam volume of distribution (Vz) was significantly smaller in cirrhotic patients than in controls (1.83 vs 2.57 l/kg), and total clearance was likewise reduced (2.15 vs 3.15 ml/min/kg). Elimination half-life was similar between groups (10.0 vs. 10.2 h). There were no significant differences between renal failure and control patients in clotiazepam Vz, oral clearance, or elimination half-life. Thus cirrhosis is associated with reduced clearance of clotiazepam, probably due to impairment of its microsomal oxidation. However clotiazepam disposition is not significantly altered in dialysis-dependent renal insufficiency patients.
AuthorsH R Ochs, D J Greenblatt, M Knüchel
JournalEuropean journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 30 Issue 1 Pg. 89-92 ( 1986) ISSN: 0031-6970 [Print] GERMANY, WEST
PMID2872061 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Azepines
  • Adult
  • Aged
  • Azepines (metabolism)
  • Female
  • Half-Life
  • Humans
  • Kidney Failure, Chronic (metabolism)
  • Kinetics
  • Liver Cirrhosis (metabolism)
  • Male
  • Middle Aged
  • Renal Dialysis

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