Kurowski M, Reim HG
[Metabolic interaction between cimetidine, ranitidine and amitriptyline/chlordiazepoxide] [Clinical Trial, English Abstract, Journal Article, Randomized Controlled Trial]
Z Gastroenterol 1986 Oct; 24(10):627-34.
The effects of cimetidine and ranitidine on plasma levels of amitriptyline and chlordiazepoxide were examined in a biphasic study with 12 young male volunteers. During the first phase all subjects received a fixed combination of 2 X amitriptyline (25 mg) and chlordiazepoxide (10 mg) daily for one week. After the last dose blood samples were drawn up to 72 hours in order to detect plasma levels of the drugs and their main metabolites. Following a wash-out-period of 7 days two groups of 6 subjects, each were formed in a randomized order. In addition to the mentioned medication 3 X 200 mg plus 1 X 400 mg of cimetidine daily or 2 X 150 mg of ranitidine daily were administered for one week. After discontinuation of amitriptyline/chlordiazepoxide the medication with H2-blockers was kept and blood samples were collected again for plasma analysis. Plasma level detections were carried out employing HPLC. The change of the area under the plasma level-time curve (AUC), total clearance and terminal half-life served as parameters indicating interaction. Under treatment with cimetidine plasma levels of amitriptyline and chlordiazepoxide were significantly (5%) increased, whereas such effects could not be observed with ranitidine. Due to these interactions under the conditions of coadministration of H2-blockers and amitriptyline and/or chlordiazepoxide the use of ranitidine is recommended.
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