Influence of age and gender on risperidone plasma concentrations

There is limited information on gender- and age-specific effects on plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone. The present study investigated dose- and weight-adjusted plasma concentrations of risperidone and its metabolite in three age groups (45 years, 45-60 years, over 60 years). Gender-specific differences were examined in the whole sample and for the premenopausal subgroup. One hundred and twenty-nine patients (18-93 years) were included in the study, 52 (40%) male and 77 (60%) female. Concentrations of risperidone and 9-hydroxyrisperidone were measured at steady-state by high-performance liquid chromatography with electrochemical detection (HPLC-ED). When total plasma concentrations (risperidone plus 9-hydroxyrisperidone) were adjusted for daily maintenance dose (ng/mL/mg C/D ratio), significant differences between all age groups were found. We found a mean increase of the C/D ratio by 34.8% per decade in patients older than 42 years. No significant sex-related differences in the average plasma concentrations were observed for the whole sample and for the premenopausal subgroup. This study shows clear evidence of higher risperidone total plasma concentrations for patients over 40 years of age. This linear increase (over 30% per decade) may then lead to an increased incidence of adverse effects in elderly patients.