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Cimetidine impairs nitrazepam clearance
Author(s) -
Ochs Hermann R,
Greenblatt David J,
Gugler Roland,
Müntefering Gerrit,
Locniskar Ann,
Abernethy Darrell R
Publication year - 1983
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.1983.157
Subject(s) - nitrazepam , cimetidine , chemistry , pharmacology , volume of distribution , drug , pharmacokinetics , medicine , diazepam
The effect of cimetidine on hepatic clearance of the benzodiazepine derivative nitrazepam was evaluated in healthy subjects. Six received a single 5‐ or 10‐mg oral nitrazepam dose in the drug‐free state and again with therapeutic cimetidine doses. Nitrazepam kinetics were determined from multiple serum concentrations measured during the 72 hr after each dose. Cimetidine had no effect on nitrazepam absorption kinetics, since peak serum nitrazepam concentration and time of peak concentration were not altered. Cimetidine did not alter nitrazepam volume of distribution, but cimetidine consistently reduced nitrazepam clearance, from a mean of 1.41 ml/min/kg in the control state to 1.17 ml/min/kg during cimetidine treatment. This resulted in prolongation of nitrazepam elimination t½ from 22.2 to 27.8 hr. Thus the ability of cimetidine to impair drug oxidation in man extends to the capacity for clearance of nitrazepam, a compound biotransformed mainly by nitroreduction. Clinical Pharmacology and Therapeutics (1983) 34 , 227–230; doi: 10.1038/clpt.1983.157