Single dose pharmacodynamics of thioridazine and remoxipride in healthy younger and older volunteers

Phenothiazines are widely used in older patients, but little experimental w ork has been carried out in this age group. Two groups of healthy volunteer s, a younger group (Y: six males and six females, aged 20-42 years) and an older group (O: six males and eight females, aged 65-77 years) took part in a randomized double-blind three-period crossover study in which they recei ved by mouth single doses of thioridazine (Y: 50 mg; O: 25 mg) remoxipride (Y: 100 mg; O: 50 mg) or placebo. Measures of central nervous system (CNS) and haemodynamic function were carried out before drug administration and a t 1.5-h intervals up to 9 h post-dose, and blood samples were collected ove r a 24-h period. No significant differences in dose-corrected pharmacokinet ic variables were found between the two groups. There was evidence of marke d CNS depressant effects of thioridazine from both objective and subjective measures. The effects for remoxipride were similar, though generally less marked. After allowance was made for dose, there was little indication of a ny difference in degree of CNS depression between the two age groups. Haemo dynamic measures showed orthostatic reductions in blood pressure with thior idazine which were particularly marked in the older group, who also showed lower compensatory increases in pulse rate. These results indicate potentia l problems with orthostatic hypotension with thioridazine in older patients . CNS depression may also be a problem, especially in patients with comprom ised cholinergic function.