TY - JOUR
T1 - Cimetidine impairs nitrazepam clearance
AU - Ochs, Hermann R.
AU - Greenblatt, David J.
AU - Gugler, Roland
AU - Müntefering, Gerrit
AU - Locniskar, Ann
AU - Abernethy, Darrell R.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1983/8
Y1 - 1983/8
N2 - 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 mllminlkg during cimetidine treatment. This resulted in prolongation of nitrazepam elimination t 1 2 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.
AB - 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 mllminlkg during cimetidine treatment. This resulted in prolongation of nitrazepam elimination t 1 2 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.
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U2 - 10.1038/clpt.1983.157
DO - 10.1038/clpt.1983.157
M3 - Article
C2 - 6872417
AN - SCOPUS:0020578035
SN - 0009-9236
VL - 34
SP - 227
EP - 230
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 2
ER -