The plasma protein binding of the new antipsychotic risperidone and of
its active metabolite 9-hydroxy-risperidone was studied in vitro by e
quilibrium dialysis. Risperidone was 90.0% bound in human plasma, 88.2
% in rat plasma and 91.7% in dog plasma. The protein binding of 9-hydr
oxy-risperidone was lower and averaged 77.4% in human plasma, 74.7% in
rat plasma and 79.7% in dog plasma. In human plasma, the protein bind
ing of risperidone was independent of the drug concentration up to 200
ng/ml. The binding of risperidone increased at higher pH values. Risp
eridone was bound to both albumin and alpha(1)-acid glycoprotein. The
plasma protein binding of risperidone and 9-hydroxy-risperidone in the
elderly was not significantly different from that in young subjects.
Plasma protein binding differences between patients with hepatic or re
nal impairment and healthy subjects were either not significant or rat
her small. The blood to plasma concentration ratio of risperidone aver
aged 0.67 in man, 0.51 in dogs and 0.78 in rats. Displacement interact
ions of risperidone and 9-hydroxy-risperidone with other drugs were mi
nimal.