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

Abstract

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 clearance 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 concentrations 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/risperidone 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.

Effects of age and gender on the serum levels of clozapine, olanzapine, risperidone, and quetiapine

“…In most previous studies (), an increase in dose‐adjusted concentrations has been found in the elderly, most often defined as those above 65 of 70 years of age, but the extent of this increase has varied considerably and there are also studies where no age‐related increases were found . In almost none of these studies, attempts have been made to divide the elderly into separate age groups.…”

“…For risperidone, no discernible influence of age on the dose‐adjusted plasma concentrations of risperidone plus its active metabolite 9‐hydroxyrisperidone was found in 95 samples from a therapeutic drug monitoring (TDM) service or in a study in 20 geriatric in‐patients . In contrast, another study found that the dose‐adjusted concentration of risperidone plus active metabolite was almost three‐fold higher in the age group above 60 than in those below 45 .…”

Modelling Age-Related Changes in the Pharmacokinetics of Risperidone and 9-Hydroxyrisperidone in Different CYP2D6 Phenotypes Using a Physiologically Based Pharmacokinetic Approach

“…All PBPK models were verified in the elderly using published clinical data of 20 geriatric inpatients aged 55 years of age or older, admitted to the inpatient programs of the Western Psychiatric Institute and Clinic (3811 O'Hara Street, Pittsburgh, PAP 15213) between November 1996 and March 1998 (29). All patients were identified through daily reviews of pharmacy records, prescribed risperidone and treated under naturalistic conditions.…”

“…There are manifold reasons for this. Firstly, all geriatric inpatients enrolled in the published investigation were treated under naturalistic conditions (29). This means, potentially concomitant medication with CYP inhibitors or inducers should be considered, since patients over the age of 65 years often suffer from several diseases.…”

“…Here, the creatinine clearance of two out of the four geriatric inpatients (patient no. 9 and 15) amounts to 25.0 mL/min/1.73m 2 and 27.5 mL/min/1.73m 2 using 8 h urine collection according to Maxwell et al (29). Apart from an inadequate measurement, both values indicate a severe decrease in glomerular filtration rate (38).…”