Pharmacokinetics of risperidone in chronic schizophrenic patients

Abstract

In a randomized, crossover study, 24 schizophrenic patients received a single 4-mg dose of risperidone in caplet or tablet form. Each of the two study periods lasted 5 days. Blood samples to determine (by radioimmunoassay) plasma levels of risperidone and its major metabolite, 9-hydroxy-risperidone (9-OH-risperidone), were obtained each day. The two formulations of risperidone were bioequivalent. Following are the mean pharmacokinetics of risperidone and risperidone + 9-OH-risperidone: area under the plasma concentration curve (AUC) from 0 to 96 hours; 278.0 and 716.9 ng.hr/mL; AUC from 0 to infinity, 291.9 and 762.4 ng.hr/mL; peak plasma concentration, 33.0 and 44.5 ng/mL; time to peak concentration, 1.39 and 1.78 hours; and elimination half-life, 14.93 and 23.04 hours. These results demonstrate that the active moiety (risperidone plus 9-OH-risperidone) has a half-life of 23 hours and reveal a pool of risperidone (terminal half-life, 14.9 hours) that may allow twice-daily or even once-daily dosing.