Metabolism of thioridazine in the elderly

Metabolism of drugs may change with age. Yet, there are few studies that provide data to help define appropriate doses of neuroleptic drugs in the treatment of the elderly. To address this issue, we determined serum concentrations of thioridazine and its active metabolites, mesoridazine and sulforidazine, by high performance liquid chromatography in young adult (mean age, 28 +/- 7.6 years) and elderly (mean age, 76 +/- 7.7 years) patients after single 25-mg oral doses of thioridazine. At both times measured, 4 and 8 hours after dosing, the concentrations of parent compound and metabolites in serum were 1.5- to twofold higher, and side effects (especially postural hypotension and dry mouth) were more frequent and severe in the elderly patients. These results, along with those reported in a small number of studies of serum drug levels during extended treatment of the elderly, support the practice of using smaller doses of phenothiazine neuroleptics in older patients.