Serum Concentrations and Side Effects in Psychiatric Patients During Risperidone Therapy

Abstract

Steady state serum concentrations of risperidone and 9-hydroxyrisperidone (9-OH-risperidone), the active moiety, were measured in 42 patients. The concentration-to-dose ratios (C/D) varied by a factor of 20, from 1.8 to 36.8 (nmol/l)/(mg/24 hours), and 90% of the active moiety was constituted of 9-OH-risperidone. No correlation between the serum concentration of the active moiety and the side effects evaluated by the UKU Side Effect Scale was found. The absence of CYP2D6 (poor metabolizers) or the coadministration of drugs other than benzodiazepines increased the ratio between parent compound and metabolite but did not significantly influence the C/D of the total active moiety. A therapeutic range for serum risperidone has not been established, but 6 mg/day is considered the optimum dose for most patients. The authors found that in 90% of 22 patients administered 6 mg/day risperidone, the serum levels were within 50 to 150 nmol/l.

Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

“…9-Hydroxyrisperidone is further metabolized by N-dealkylation, possibly by CYP3A (Spina et al, 2000). The ratio of risperidone to 9-hydroxyrisperidone concentrations is Ͻ1 in EMs, and Ͼ1 in PMs, but the sum of active moieties is similar (Mannens et al, 1993;Nyberg et al, 1995a;Olesen et al, 1998;Scordo et al, 1999;Roh et al, 2001b;Bondolfi et al, 2002). UMs have very low ratios of risperidone to 9-hydroxyrisperidone (Guzey et al, 2000).…”

Possible Relationship between Combined Plasma Concentrations of Risperidone plus 9-Hydroxyrisperidone and Extrapyramidal Symptoms

“…Risperidone is extensively metabolized in the liver by cytochrome P450 3A4 as well as 2D6 into a major active metabolite, 9-hydroxyrisperidone [12,13], which is the predominant circulating molecule and appears to be of approximately equal efficacy as the parent compound with respect to receptor-binding activity and some of its effects on animals [14]. Therefore, the plasma concentration of active moiety is the sum of the plasma concentrations of ripseridone and 9-hydroxyrisperidone [15].…”

Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort

“…Several studies investigated the relationship between neurologic symptoms and plasma concentration, with positive [64,1,28,27] or negative results [30,29,31] . In the present study, C min-active moiety was significantly associated with akathisia, tremor and combined with rigidity.…”

“…Conflicting results were however obtained in several studies examining the relationship between risperidone or 9-hydroxyrisperidone concentrations with neurological toxicity [28][29][30][31] .…”