A systematic review and combined analysis of therapeutic drug monitoring studies for long-acting risperidone. Issue 9 (2nd September 2017)

• Record Type: Journal Article
• Authors: Schoretsanitis, Georgios; Spina, Edoardo; Hiemke, Christoph; de Leon, Jose
• Is Part Of: Expert review of clinical pharmacology. Volume 10:Issue 9(2017)
• Page Start: 965
• Page End: 981
• Publication Date: 2017-09-02
• Subjects: Antipsychotic agents/administration & dosage -- delayed-action preparations -- drug monitoring -- injections -- risperidone/administration & dosage -- risperidone/blood -- risperidone/metabolism -- risperidone/pharmacokinetics -- risperidone/pharmacology -- risperidone/therapeutic use -- schizophrenia/drug therapy; Clinical pharmacology -- Periodicals; 615.105
• DOI: 10.1080/17512433.2017.1345623
• Languages: English
• ISSNs: 1751-2433

Abstract

ABSTRACT: Introduction : This systematic review of therapeutic drug monitoring (TDM) identifies three long-acting injectable (LAI) risperidone formulations. Areas covered : Limited data is available on two formulations (RBP-7000 and in Situ Microparticle), but 20 TDM articles on the microsphere formulation were found. Risperidone TDM includes the serum concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, used for calculating: 1) the risperidone/9-hydroxyrisperidone (R/9-OH-R) ratio (a measure of CYP2D6; values >1 are indicative of a CYP2D6 poor metabolizer) and 2) the total risperidone concentration-to-dose (C/D) ratio (a measure of risperidone clearance with a normal value around 7 in oral risperidone). The weighted mean R/9-OH-R ratio was 0.48 (approximately twice that of oral risperidone TDM) in a combined analysis from 329 patients in 6 risperidone LAI studies without major confounders. The total C/D ratios from 297 patients in 6 risperidone LAI studies ranged from 7.4 to 9.7 ng/ml/mg/day with a weighted mean of 8.8 ng/ml/mg/day. Expert commentary : Clinicians using TDM for risperidone LAI microsphere formulation need to: 1) consider steady state to be reached ≥ 6 weeks after the first injection, 2) pay attention to a) co-medications with inducers/inhibitors, b) severe inflammations/infections, and c) hepatic/renal impairment, and 3) use Castberg's recommendation to calculate risperidone dosing.