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Influence of cimetidine on oral diazepam elimination with measurement of subsequent cognitive change.
Author(s) -
Gough PA,
Curry SH,
Araujo OE,
Robinson JD,
Dallman JJ
Publication year - 1982
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1982.tb04966.x
Subject(s) - diazepam , cimetidine , digit symbol substitution test , crossover study , pharmacokinetics , placebo , oral administration , pharmacology , visual analogue scale , medicine , chemistry , anesthesia , alternative medicine , pathology
In a double‐blind crossover design, the effect of cimetidine on oral diazepam pharmacokinetics and an evaluation of cognitive function change was studied in seven healthy volunteers. Subjects randomly received placebo or cimetidine 300 mg orally every 6 h for a total of five doses prior to diazepam 10 mg. A significant increase in diazepam elimination half‐life from (mean +/‐ s.e. mean) 66.9 +/‐ 21.4 to 89.6 +/‐ 22.5 h (P = 0.006) and area under the plasma concentration‐time curve from 5.06 +/‐ 1.47 to 8.93 +/‐ 1.88 micrograms ml‐1 h (P = 0.028) was observed indicating a probable cimetidine induced inhibition of diazepam hepatic metabolism. Digit symbol substitution and visual analogue scales were used to measure the effect of an alteration of diazepam kinetics on cognitive function. An enhancement of pharmacological effect as reflected in digit symbol substitution scores and visual analogue scale measurements was not observed.