Serum Concentrations of Risperidone and 9-Hydroxyrisperidone After Administration of the Long-Acting Injectable Form of Risperidone

Abstract

There is limited documentation on the pharmacokinetics of long-acting intramuscular risperidone in a naturalistic setting. The objective of this study was to investigate the concentrations of risperidone and its active metabolite 9-hydroxyrisperidone as well as the concentration/dose (C/D) ratios achieved after intramuscular depot administration in a routine therapeutic drug monitoring setting. Thirty samples were collected from 10 female and 20 male patients receiving depot injections of risperidone. For 6 of the patients, the results could be compared with corresponding data available after previous oral administration of risperidone. In addition, data from a group of 278 patients using oral risperidone were retrieved. The median serum concentrations of risperidone plus 9-hydroxyrisperidone were 38 nmol/L 12-14 days after a intramuscular dose of 25 mg/14 days, 67 nmol/L after a dose of 37.5 mg/14 days, 99 nmol/L after a dose of 50 mg/14 days, and 148 nmol/L after a dose of 75 mg/14 days. The median C/D ratio for risperidone plus 9-hydroxy-risperidone was 22.2 (nmol/L)/(mg/d). In the group on oral medication, the median C/D ratio was 18.6 (nmol/L)/(mg/d). In the 6 patients previously using oral risperidone, switching to depot injections gave an average increase of 33% (range 12%-68%) in the C/D ratio. In conclusion, the authors' data indicate that there are great interindividual differences in the extent to which the daily dose has to be reduced when switching from oral to intramuscular depot administration to achieve the same serum concentrations of risperidone plus 9-hydroxyrisperidone. Because the degree of dose adjustment required for the individual patient so far cannot be predicted, guidance by therapeutic drug monitoring might be helpful.

Long-acting injectable risperidone and metabolic ratio: a possible index of clinical outcome in treatment-resistant schizophrenic patients

“…We found lower mean plasma concentrations of RSP and its active metabolite than those described in previous studies but was confirmed the considerable inter-individual variability of plasma drug levels affected by physiological, genetic and environmental factors (Castberg and Spigset 2005;Nesvag et al 2006). The relationship between plasma RSP levels and clinical response has been investigated in the case of oral RSP administration, with conflicting results (Riedel et al 2005;Mauri et al 2001;Olesen et al 1998;Spina et al 2001;Odou et al 2000): some authors have found no relationship (Spina et al 2001;Verma et al 2005), but Odou et al (2000) found that the efficacy of RSP significantly increased at plasma active moiety levels between 25 and 150 μg/L, and Mauri et al (2001) observed that a greater improvement in PANSS was associated with plasma active moiety levels of 15-30 ng/mL.…”

“…The studies based on the therapeutic drug monitoring of RLAI did not consider clinical variables, and so it is difficult to draw any useful conclusions for clinical practice (Castberg and Spigset 2005;Nesvag et al 2006;Mannaert et al 2005).…”

“…NR = non-responder R = responder plasma concentrations of RSP and its 9-OH-RSP metabolite (the active moiety) without taking into account the potential differences between the two drugs (Castberg and Spigset 2005;Olesen et al Olesen et al 1998;Odou et al 2000). On the contrary, our preliminary results seem to indicate that the plasma concentrations of the active moiety may be a rather poor indicator of the antipsychotic potency of RSP unless the ratio of its component parts is also considered.…”

“…Plasma concentrations of free RSP increase gradually, peak after about 5 weeks, and can still be detected up to 7 weeks after a single intramuscular injection (Mauri et al 2007). Steady state is reached after the fourth of regular fortnightly injections (Castberg and Spigset 2005).…”

Effects of Depth of Needle Insertion with Risperidone Long-Acting Injectable in Persons with Schizophrenia: A Randomized Double-Blind Study

“…Despite its common use, there is limited documentation available on its pharmacokinetics in a naturalistic setting [22]. Only recently, a paper was published in which the 9-OH-RIS concentration of RLAI was measured and its relationship with injection needle Group-D: 50 mm needle inserted group, Group-S: 20mm needle inserted group.…”