Risperidone is the only second-generation (atypical) antipsychotic medication available in a long-acting injectable formulation. The mechanism of drug delivery and the pharmacokinetics of this medication are distinctively different from the first-generation injectable depot medications. Antipsychotic blood levels have been reported in carefully managed single-dose and multiple-dose studies of long-acting risperidone. However, there have been no studies of blood levels produced by the variability in doses and schedules that may occur in clinical practice. Mathematical modeling allows for estimation of blood levels in a variety of clinical scenarios that have yet to be studied empirically. This paper presents mathematically modeled representations of antipsychotic blood levels in clinical situations with long-acting risperidone, with the goal of helping professionals, patients, and family members make informed decisions regarding treatment.
A model of single-dose pharmacokinetics was derived from a published, empirical single-dose study. The model was used to prepare graphs of expected multiple-dose schedules consistent with clinical situations, using empirically validated assumptions.
The model was validated by comparison of the results of multiple-dose modeling with published empirical multi-dose data. Graphs of expected blood levels in several clinical situations are presented. Future empirical studies are required to fully validate these results.
Mathematical models of antipsychotic blood levels in various common situations allow a better appreciation of the novel pharmacokinetics of long-acting injectable risperidone, which may lead to more informed decision-making.
WILSON: Oregon Health & Science University.
Please send correspondence and reprint requests to: William H. Wilson, MD, Oregon Health & Science University, UHN80 OHSU, 3181 SW Sam Jackson Park Road, Portland, OR 97239.
This work was presented as a poster in October 2004 at the American Psychiatric Association’s 56th Institute on Psychiatric Services. No financial support was received for this project (poster and article) from any pharmaceutical company.