Interaction of H2-receptor antagonists and benzodiazepine sedation. A double-blind placebo-controlled investigation of the effects of cimetidine and ranitidine on recovery after intravenous midazolam.
H2-receptor antagonists differentially inhibit cytochrome P450 and this may affect the rate at which benzodiazepines are metabolised. However, it is not known whether this delayed clearance results in prolonged psychomotor impairment. In a randomised double-blind trial 28 healthy volunteers received two single doses of midazolam (0.07 mg.kg-1) at an interval of one week during which they took cimetidine 400 mg, ranitidine 150 mg or placebo, each twice daily. Recovery from the benzodiazepine was monitored on each occasion over a 12 h period using a battery of psychometric tests. There was wide individual variation in performance; however, an overall measure of impairment indicated a significant difference at 2.5 h (p < 0.05), the cimetidine group having a high impairment score. This decrement appeared to be in cognitive and psychomotor functions and was not reflected in the subjective assessment.
Department of Anaesthetics, University of Wales, College of Medicine, Cardiff.
L D
LD
Sanders
C
C
Whitehead
C D
CD
Gildersleve
M
M
Rosen
J O
JO
Robinson
D000293:Adolescent; D000328:Adult; D002927:Cimetidine / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D008568:Memory / Q000187:drug effects; D008874:Midazolam / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D011899:Ranitidine / Q000494:pharmacology*; D013997:Time Factors
D006993:Hypnotics and Sedatives; D002927:Cimetidine; D011899:Ranitidine; D008874:Midazolam