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Influence of renal failure on the kinetics of zimeldine and norzimelidine.

Abstract
The kinetics of zimeldine (Z) and its demethylated metabolite, norzimelidine (NZ), were determined after administration of a single 200 mg oral dose of Z to 6 healthy volunteers (Group I), and to patients with mild (Group II) and severe renal failure (Group III). Z and NZ concentrations were assayed by HPLC in serial plasma and urine samples over 6 days following the dose. In Group I Z was rapidly absorbed and metabolized into NZ, and then the plasma concentrations declined with apparent elimination half-lives of 8.4 h and 24.9 h for Z and NZ respectively, whilst the renal clearance of both compounds was low, Z 15.7 ml/min and NZ 33.0 ml/min. The plasma level of Z differed little between Groups I and III, but the area under the curve was significantly higher in Group III than in Group I subjects (AUC0-144 = 17.3 and 6.8 mumol X l-1 X h, respectively). Severe renal failure did not affect the peak plasma concentration of NZ but it did significantly increase peak time, apparent elimination half-life, and the area under the plasma concentration curve. A significant inverse relationship was found between renal clearance of NZ and plasma creatinine. Since NZ is as pharmacologically potent as Z, the results suggest that the dose of Z should be reduced in patients with severe renal insufficiency.
AuthorsN Ferry, G Cuisinaud, P Cochat, N Pozet, P Y Zech, J Sassard
JournalEuropean journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 28 Issue 4 Pg. 453-6 ( 1985) ISSN: 0031-6970 [Print] Germany
PMID3161742 (Publication Type: Journal Article)
Chemical References
  • Antidepressive Agents
  • Zimeldine
  • norzimelidine
Topics
  • Adult
  • Antidepressive Agents (metabolism)
  • Female
  • Humans
  • Kidney (metabolism)
  • Kidney Diseases (metabolism)
  • Kinetics
  • Male
  • Middle Aged
  • Zimeldine (analogs & derivatives, metabolism)

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