Risperdal

[Risperidone]

Food Effect

Food does not affect either the rate or extent of absorption of risperidone. Thus, risperidone can be given with or without meals.

Distribution

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Risperidone is rapidly distributed. The volume of distribution is 1-2 L/ kg. In plasma, risperidone is bound to albumin and 1 -acid glycoprotein. The plasma protein binding of risperidone is 90% , and that of its major metabolite, 9-hydroxyrisperidone, s 77% .

Neither risperidone nor 9-hydroxyrisperidone displaces each other from plasma binding sites. High therapeutic concentrations of sulfamethazine ( 100 mcg/ mL) , warfarin ( 10 mcg/ mL) , and carbamazepine ( 10 mcg/ mL) caused only a slight ncrease in the free fraction of risperidone at 10 ng/ mL and 9-hydroxyrisperidone at 50 ng/ mL, changes of unknown clinical significance.

Metabolism

Risperidone is extensively metabolized in the liver. The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by the enzyme, CYP 2D6. A minor metabolic pathway is through N -dealkylation. The main metabolite, 9-hydroxyrisperidone, has similar pharmacological activity as risperidone. Consequently, the clinical effect of the drug ( e. g. , the active moiety) results from the combined concentrations of risperidone plus 9-hydroxyrisperidone.

CYP 2D6, also called debrisoquin hydroxylase, is the enzyme responsible for metabolism of many neuroleptics, antidepressants, antiarrhythmics, and other drugs. CYP 2D6 is subject to genetic polymorphism ( about 6% -8% of Caucasians, and a very low percentage of Asians, have little or no activity and are poor metabolizers ) and to inhibition by a variety of substrates and some non-substrates, notably quinidine. Extensive CYP 2D6 metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, whereas poor CYP 2D6 metabolizers convert it much more slowly. Although extensive metabolizers have lower risperidone and higher 9-hydroxyrisperidone concentrations than poor metabolizers, the pharmacokinetics of the active moiety, after single and multiple doses, are similar in extensive and poor metabolizers.

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