Cimetidine does not influence the metabolism of the H1-receptor antagonist ebastine to its active metabolite carebastine.
Ebastine is an H1-receptor antagonist with a relative lack of sedating properties. It is almost completely converted to carebastine, and it is this metabolite which is responsible for the antihistaminic effect. Twelve healthy subjects received a single 20 mg dose of ebastine on day 2 of a multiple oral dosing regimen of either cimetidine (400 mg three times daily and 800 mg in the evening on the day preceding ebastine administration and 400 mg four times daily on the 2 following days) or placebo in a randomised cross-over design. Significant plasma concentrations of ebastine were not detected after either treatment. The AUC of carebastine was not affected by cimetidine coadministration (4049 +/- 985 ng ml-1 h after cimetidine vs 3795 +/- 959 ng ml-1 h after placebo; 95% confidence interval of the difference: -412 to 919). Cimetidine coadministration did not induce any effect of ebastine on blood pressure and heart rate or cause sedation.
Van Rooij
J
J
Centre for Human Drug Research, Leiden University Hospital, The Netherlands.
Schoemaker
H C
HC
Bruno
R
R
Reinhoudt
J F
JF
Breimer
D D
DD
Cohen
A F
AF
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002090:Butyrophenones / Q000009:adverse effects / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000009:adverse effects / Q000494:pharmacology*; D004347:Drug Interactions; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics*
D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; C058251:carebastine; D002927:Cimetidine; C058249:ebastine