THE INFLUENCE OF CIMETIDINE ON THE DISPOSITION KINETICS OF THE ANTIDEPRESSANT VENLAFAXINE

The influence of cimetidine on the disposition pharmacokinetics of the antidepressant drug, venlafaxine, and its active metabolite, O-desmet hylvenlafaxine, was examined in 18 healthy young men and women. The st eady-state pharmacokinetic profiles of venlafaxine and O-desmethylvenl afaxine were evaluated during a 24-hour period after 5 days of treatme nt with venlafaxine (50 mg three times a day) and during a second 24-h our period after 5 days of combination treatment with venlafaxine (50 mg three times a day) and cimetidine (800 mg once a day). The apparent oral clearance of venlafaxine decreased significantly in the presence of cimetidine and the average steady-state plasma concentration of ve nlafaxine increased significantly in the presence of cimetidine, but t here were no changes in the corresponding concentrations of the active metabolite. However, O-desmethylvenlafaxine exhibits pharmacologic ac tivity that is approximately equimolar to that of venlafaxine, and the sum of venlafaxine plus O-desmethylvenlafaxine plasma concentrations was increased by an average of only 13%. Therefore, the effect of cime tidine coadministration is not expected to result in clinically import ant alterations in the response to venlafaxine in patients with depres sion. This may not be true, however, for patients with compromised hep atic metabolic function. (C) 1998 The American College of Clinical Pha rmacology.