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dc.contributor.authorUchida, Hiroyuki-
dc.contributor.authorMamo, David-
dc.contributor.authorPollock, Bruce G.-
dc.contributor.authorSuzuki, Takefumi-
dc.contributor.authorTsunoda, Kenichi-
dc.contributor.authorWatanabe, Koichiro-
dc.contributor.authorMimura, Masaru-
dc.contributor.authorBies, Robert R.-
dc.identifier.citationUchida, H., Mamo, D. C., Pollock, B. G., Suzuki, T., Tsunoda, K., Watanabe, K., ... & Bies, R. R. (2012). Predicting plasma concentration of risperidone associated with dosage change: a population pharmacokinetic study. Therapeutic Drug Monitoring, 34(2), 182-187.en_GB
dc.description.abstractBackground: Due to high interindividual variability in peripheral pharmacokinetic parameters, dosing of antipsychotics relies on clinical trial and error. This blind process of upward or downward clinical dose titration carries a risk of relapse and adverse effects in the treatment of schizophrenia. Using population pharmacokinetic methods, the authors therefore sought to predict plasma concentrations of risperidone (RIS) plus 9-hydroxyrisperidone (9-OH-RIS) before a dosage change. Methods: Two plasma samples were collected at 2 separate given time points for the measurement of RIS and 9-OH-RIS concentrations from 50 patients with schizophrenia or schizoaffective disorder maintained on risperidone (mean ± SD age = 56 ± 15 years; 39 men). After an oral risperidone dose adjustment, a third sample was collected. The plasma concentration of the third sample was individually predicted in a blinded fashion with the 2 baseline plasma concentrations before dose adjustment and clinical and demographic information, using the mixed-effects model with NONMEM that was derived from the data of the Clinical Antipsychotic Trials in Intervention Effectiveness study. Results: The mean (95% confidence interval) prediction errors (in ng/mL) were as low as 0.0 (−1.3 to 1.4) for RIS and 1.0 (−1.1 to 3.0) for 9-OH-RIS. The observed and predicted concentrations of RIS and 9-OH-RIS were highly correlated (r = 0.96, P < 0.0001 and r = 0.92, P < 0.0001, respectively). Conclusions: Antipsychotic plasma concentrations can be predicted before risperidone dose adjustment. In light of the known relationship between plasma drug concentration, dopamine D2 receptor occupancy, and clinical effects, our results confirm that individualized dosing with the measurement of antipsychotic plasma concentrations has the potential for bedside clinical application.en_GB
dc.publisherLippincott Williams & Wilkinsen_GB
dc.subjectAntipsychotic drugsen_GB
dc.titlePredicting plasma concentration of risperidone associated with dosage change : a population pharmacokinetic studyen_GB
dc.rights.holderThe copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holderen_GB
dc.publication.titleTherapeutic Drug Monitoringen_GB
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