Predicting plasma concentration of risperidone associated with dosage change

A population pharmacokinetic study

Hiroyuki Uchida, David C. Mamo, Bruce G. Pollock, Takefumi Suzuki, Kenichi Tsunoda, Koichiro Watanabe, Masaru Mimura, Robert Bies

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: 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.

Original languageEnglish
Pages (from-to)182-187
Number of pages6
JournalTherapeutic Drug Monitoring
Volume34
Issue number2
DOIs
StatePublished - Apr 2012

Fingerprint

Risperidone
Pharmacokinetics
Population
Social Adjustment
Antipsychotic Agents
Schizophrenia
Clinical Trials
Dopamine D2 Receptors
Psychotic Disorders
Demography
Confidence Intervals
Recurrence
hydroxide ion

Keywords

  • antipsychotic
  • population pharmacokinetics
  • prediction
  • risperidone
  • schizophrenia

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Predicting plasma concentration of risperidone associated with dosage change : A population pharmacokinetic study. / Uchida, Hiroyuki; Mamo, David C.; Pollock, Bruce G.; Suzuki, Takefumi; Tsunoda, Kenichi; Watanabe, Koichiro; Mimura, Masaru; Bies, Robert.

In: Therapeutic Drug Monitoring, Vol. 34, No. 2, 04.2012, p. 182-187.

Research output: Contribution to journalArticle

Uchida, Hiroyuki ; Mamo, David C. ; Pollock, Bruce G. ; Suzuki, Takefumi ; Tsunoda, Kenichi ; Watanabe, Koichiro ; Mimura, Masaru ; Bies, Robert. / Predicting plasma concentration of risperidone associated with dosage change : A population pharmacokinetic study. In: Therapeutic Drug Monitoring. 2012 ; Vol. 34, No. 2. pp. 182-187.
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