Serum concentrations of paliperidone versus risperidone and clinical effects

The major aim of this multicenter retrospective analysis was to examine the relationship between paliperidone serum concentrations and clinical effects in patients treated with this new antipsychotic drug. Intra-individual variability in trough serum concentrations was also analyzed in patients under treatment with either the paliperidone-extended release (ER) formulation or the risperidone immediate-release formulation.

Data were obtained from 217 patients of four medical centers who were being followed by therapeutic drug monitoring (TDM). Serum concentrations were associated with clinical response using Clinical Global Impressions (CGI) scores.

The mean concentration of paliperidone was 36 +/- 25 ng/ml, and the mean dose corrected concentration (C/D) was 4.7 +/- 2.9 ng/ml/mg. Among patients receiving paliperidone as antipsychotic monotherapy and who showed at least a much improved level according to the CGI scores, the 25th-75th percentiles of paliperidone concentrations were 20-52 ng/ml; these were very similar to the recommended therapeutic range of 20-60 ng/ml for risperidone plus 9-hydroxy-risperidone (active moiety). In 13 patients treated with paliperidone ER and 17 patients treated with risperidone, all of whom had repeated drug measurements, the intra- and inter-individual variabilities of trough serum concentrations were similar for the paliperidone and risperidone active moiety, ranging between 30 and 35%.

Based on these results, we conclude that risperidone and paliperidone have a similar therapeutic range and similar intra-individual variability in terms of trough serum levels. For treatment optimization, monitoring of plasma concentrations may be as useful for paliperidone as for risperidone.