Effect of cimetidine on the pharmacodynamics, pharmacokinetics and biotransformation of a single oral dose of alpidem.
Alpidem is a new imidazopyridine derivative acting as an anxiolytic which may be prescribed with H2 receptor antagonists in patients with peptic ulcer. An open trial design (cimetidine, 1 g daily for 22 days) was carried out in eight healthy subjects. Alpidem, 50 mg was administered orally at 09:00 prior to any treatment and on days 2 and 18 of the cimetidine treatment period. Antipyrine clearance was also determined before and on day 21. Under these experimental conditions, the inhibitory effect of cimetidine on the cyt. P-450 monooxygenase system has been demonstrated (reduced clearance of antipyrine and its three main urinary metabolites) but the plasma pharmacokinetics of alpidem and its three main plasma metabolites did not appear to be modified. Alpidem induced no sedative effect but there was an insignificant trend to impair slightly the psychometric tests 1 h post-drug by the combination with cimetidine. Pharmacokinetic and pharmacodynamic evaluations did not show significant interactions with cimetidine following alpidem 50 mg administration.
Desager
J P
JP
Laboratoire de Pharmacothérapie, Université Catholique de Louvain, Brussels, Belgium.
Hulhoven
R
R
Harvengt
C
C
Bianchetti
G
G
D000284:Administration, Oral; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000983:Antipyrine / Q000493:pharmacokinetics; D001711:Biotransformation; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011594:Psychometrics; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D014151:Anti-Anxiety Agents; D007093:Imidazoles; D011725:Pyridines; D002927:Cimetidine; D006899:Mixed Function Oxygenases; C052036:alpidem; D000983:Antipyrine