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Titolo:
Pharmacokinetic-pharmacodynamic modeling of risperidone effects on electroencephalography in healthy volunteers
Autore:
Lee, DY; Lee, KU; Kwon, JS; Jang, IJ; Cho, MJ; Shin, SG; Woo, JI;
Indirizzi:
Seoul Natl Univ, Coll Med, Dept Psychiat, Seoul 110744, South Korea Seoul Natl Univ Seoul South Korea 110744 hiat, Seoul 110744, South Korea Seoul Natl Univ, Inst Neurosci, Seoul 110744, South Korea Seoul Natl UnivSeoul South Korea 110744 osci, Seoul 110744, South Korea Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul, South Korea Seoul Natl Univ Seoul South Korea d, Dept Pharmacol, Seoul, South Korea
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 3, volume: 144, anno: 1999,
pagine: 272 - 278
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; SCHIZOPHRENIC-PATIENTS; HALOPERIDOL; ANESTHESIA; MIDAZOLAM; DIAZEPAM; PLACEBO; PLASMA;
Keywords:
risperidone; 9-hydroxyrisperidone; antipsychotic; pharmacokinetic; EEG; pharmacokinetic-pharmacodynamic model; PK-PD;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Woo, JI Seoul Natl Univ, Coll Med, Dept Psychiat, 28 Yongon Dong, Seoul 110744, South Korea Seoul Natl Univ 28 Yongon Dong Seoul South Korea 110744 uth Korea
Citazione:
D.Y. Lee et al., "Pharmacokinetic-pharmacodynamic modeling of risperidone effects on electroencephalography in healthy volunteers", PSYCHOPHAR, 144(3), 1999, pp. 272-278

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 I 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 tvas postulated. All curve fittings were done with the nonlinear 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 (C-p) versus EEG effect for each subject. A linear model adequately described the relationship between the effect compartment concentrations (C-e) and EEG effects, and the two limbs of hysteresis in the C-p-effect plot were collapsed in the C-e-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. Thelinear PK-PD model fit well with the relationship between effect compartment concentrations (C-e) and EEG effects of risperidone.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 06:18:26