THE PHARMACOKINETICS OF RISPERIDONE IN HUMANS - A SUMMARY

Risperidone is rapidly and completely absorbed after oral administrati on; less than 1% is excreted unchanged in the feces. The principal met abolite was found to be 9-hydroxyrisperidone. Hydroxylation of risperi done is subject to the same genetic polymorphism as debrisoquine and d extromethorphan. In poor metabolizers the half-life of risperidone was about 19 hours compared with about 3 hours in extensive metabolizers. However, because the pharmacology of 9-hydroxy-risperidone is very si milar to that of risperidone, the half-life for the ''active fraction' ' (risperidone + 9-hydroxyrisperidone) was found to be approximately 2 0 hours in extensive and poor metabolizers. We found that risperidone exhibited linear elimination kinetics and that steady state was reache d within 1 day for risperidone and within 5 days for the active fracti on.