Psychopharmacology

, Volume 144, Issue 3, pp 272–278

Pharmacokinetic-pharmacodynamic modeling of risperidone effects on electroencephalography in healthy volunteers

  • Dong Young Lee
  • Kang Uk Lee
  • Jun Soo Kwon
  • In Jin Jang
  • Maeng Je Cho
  • Sang Goo Shin
  • J. I. Woo
ORIGINAL INVESTIGATION

DOI: 10.1007/s002130051003

Cite this article as:
Lee, D., Lee, K., Kwon, J. et al. Psychopharmacology (1999) 144: 272. doi:10.1007/s002130051003

Abstract

Rationale: CNS-active drugs produce specific electroencephalographic changes and the concentration-effect relationship of antipsychotics may be elucidated by adopting electroencephalography (EEG) as an effect measurement tool. Objective: The purpose of the present study was to determine the concentration-effect relationship of risperidone by assessing the EEG effect after oral administrations of single dose risperidone in healthy young males. Methods: Nine healthy male volunteers received a 1 mg single oral dose of risperidone according to a placebo controlled crossover design. Plasma levels of risperidone and its active metabolite 9-hydroxyrisperidone were measured by radioimmunoassay. Quantitative EEG parameters were obtained for each of four frequency bands through spectral EEG analysis. The difference in the absolute power in the delta frequency band for the F3 lead between risperidone and placebo was used as a drug effect parameter. For pharmacokinetic-pharmacodynamic modeling, the hypothetical effect compartment kinetically linked to plasma by a first-order process was postulated. All curve fittings were done with the non-linear curve-fitting program NONLIN. Results: Our results showed that absolute powers in delta and theta frequency bands were higher for risperidone administration than for placebo at all EEG leads, and the maximum effects were detected at about 3 h after administration of the drug. The hysteresis loop was observed in the plot of plasma concentration of risperidone or sum of risperidone and 9-hydroxyrisperidone (Cp) versus EEG effect for each subject. A linear model adequately described the relationship between the effect compartment concentrations (Ce) and EEG effects, and the two limbs of hysteresis in the Cp-effect plot were collapsed in the Ce-effect plot for risperidone or risperidone plus 9-hydroxyrisperidone. Conclusion: The increases of absolute power for delta and theta frequency bands of EEG were induced by single oral administration of risperidone. The linear PK-PD model fit well with the relationship between effect compartment concentrations (Ce) and EEG effects of risperidone.

Key words Risperidone 9-Hydroxyrisperidone Antipsychotic Pharmacokinetic EEG Pharmacokinetic-pharmacodynamic model PK-PD 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Dong Young Lee
    • 1
  • Kang Uk Lee
    • 1
  • Jun Soo Kwon
    • 2
  • In Jin Jang
    • 3
  • Maeng Je Cho
    • 2
  • Sang Goo Shin
    • 3
  • J. I. Woo
    • 1
  1. 1.Department of Psychiatry, Seoul National University College of Medicine & Institute for Neuroscience, 28 Yongon-Dong Chongno-Gu, Seoul 110-744, Korea Fax: +82-2-762-3176KR
  2. 2.Department of Psychiatry, Seoul National University College of Medicine, Seoul, KoreaKR
  3. 3.Department of Pharmacology, Seoul National University College of Medicine, Seoul, KoreaKR

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