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Elevation of steady‐state diazepam levels by cimetidine
Author(s) -
Klotz Ulrich,
Reimann Ingrid
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.196
Subject(s) - cimetidine , diazepam , concomitant , steady state (chemistry) , chemistry , placebo , pharmacokinetics , pharmacology , medicine , alternative medicine , pathology
The effect of cimetidine (1000 mg/day) on steady‐state diazepam (5 mg/day) kinetics was investigated in six healthy subjects. During placebo‐controlled treatment for 11 days, trough steady‐state plasma levels were 130 ± 33 ng/ml and steady‐state concentration averaged 185 ±57 ng/ml (x̄ ± SD). During concomitant treatment with diazepam and cimetidine these concentrations rose to 194 ± 52 ng/ml and 255 ± 46 ng/ml (P < 0.002). The 40% to 50% increase was due to reduction (P = 0.026) of total body clearance from 20.9 ± 9.5 ml/min (control) to 14.0 ± 3.0 ml/min (with cimetidine). Diazepam elimination half‐life was also prolonged (P = 0.02, from 39.5 ± 16.6 hr to 101 ± 58.1 hr) by cimetidine. Clinical Pharmacology and Therapeutics (1981) 30, 513–517; doi: 10.1038/clpt.1981.196