Serum concentrations and side effects in psychiatric patients during risperidone therapy

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Psychiatric Drug Monitoring

Background:

• Risperidone is an atypical antipsychotic used to treat various psychiatric conditions.
• Understanding its pharmacokinetics, including serum concentrations and metabolite ratios, is crucial for optimizing patient outcomes.
• Individual variability in drug metabolism can significantly impact therapeutic efficacy and side effect profiles.

Purpose of the Study:

• To investigate the steady-state serum concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone (9-OH-risperidone).
• To assess the concentration-to-dose (C/D) ratios and factors influencing them.
• To explore the relationship between serum levels and side effects using the UKU Side Effect Scale.

Main Methods:

• Serum samples were collected from 42 patients treated with risperidone.
• Concentrations of risperidone and 9-OH-risperidone were measured to determine the active moiety.
• Concentration-to-dose (C/D) ratios were calculated, and correlations with side effects were analyzed.

Main Results:

• A significant variation in C/D ratios (1.8 to 36.8 (nmol/l)/(mg/24 hours)) was observed.
• 9-OH-risperidone constituted approximately 90% of the active moiety.
• No correlation was found between active moiety serum concentration and side effects.
• CYP2D6 poor metabolizer status or coadministration of non-benzodiazepine drugs altered the parent compound to metabolite ratio but not the total active moiety C/D.

Conclusions:

• Significant inter-individual variability exists in risperidone pharmacokinetics.
• While a therapeutic range is not established, serum levels of 50-150 nmol/l were achieved in 90% of patients on 6 mg/day.
• Factors like CYP2D6 status influence metabolite ratios but not overall drug exposure.