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Risperidone and 9-Hydroxyrisperidone Concentrations Are Not Dependent on Age or Creatinine Clearance among Elderly Subjects

Robert A. Sweet, MD

Benoit H. Mulsant, MD

Jules Rosen, MD

Margaret A. Kirshner, BA

Kari B. Kastango, MS

Bruce G. Pollock, MD, PhD

Risperidone is extensively metabolized to an active metabolite, 9-hydroxyrisperidone (9-OH), which is dependent on renal clearance. Risperidone and 9-OH clearances are reduced in the elderly when compared to young subjects. The objective of this study was to determine whether among elderly subjects, risperidone and 9-OH clearance would further decline with increasing age and decreasing creatinine clearance (CrCl). Twenty geriatric inpatients were evaluated in a naturalistic setting with regard to total daily risperidone dose and dosing interval. Creatinine clear ance was determined using an 8-hour urine collection. Risperidone and 9-OH concentrations were determined by radioimmunoassay. Spearman's correlation coefficients were used to examine the impact of age and CrCl on con centrations of risperidone, 9-OH, their sum, and the quotient of 9-OH/risperidone. Mean age was 76.4 ± 9 years (range 56-91). Mean CrCl was 55.4 ± 32.8 mL/min/1.73 m² (range 17-142 mL/min/1.73 m²). Mean risperidone daily dose was 1.3 ± 0.7 mg. Steady-state risperidone and 9-OH concentrations were 4.1 ± 5.3 ng/mL and 9.1 ± 6.2 ng/mL, respectively. Mean 9-OH/risperidone was 6.2 ± 6.1. Concentrations of risperidone, 9-OH, their sum, and 9-OH/risperi done were not significantly correlated with age or CrCl. These results were unchanged when concentrations were corrected for total daily risperidone dose. Among elderly subjects, risperidone and 9-OH clearance do not decline with increasing age or declining CrCl. (J Geriatr Psychiatry Neurol 2002; 15:77-81).

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