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Titolo:
PLASMA-CONCENTRATIONS OF RISPERIDONE AND ITS 9-HYDROXY METABOLITE ANDTHEIR RELATIONSHIP TO DOSE IN SCHIZOPHRENIC-PATIENTS - SIMULTANEOUS DETERMINATION BY A HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH ELECTROCHEMICAL DETECTION
Autore:
ARAVAGIRI M; MARDER SR; WIRSHING D; WIRSHING WC;
Indirizzi:
UNIV CALIF LOS ANGELES,PSYCHOPHARMACOL UNIT LOS ANGELES CA 90024
Titolo Testata:
Pharmacopsychiatry
fascicolo: 3, volume: 31, anno: 1998,
pagine: 102 - 109
SICI:
0176-3679(1998)31:3<102:PORAI9>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTIPSYCHOTIC-DRUGS; RECEPTOR-BINDING; D-2; 9-HYDROXYRISPERIDONE; PHARMACOKINETICS; EXCRETION; 5-HT2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
28
Recensione:
Indirizzi per estratti:
Citazione:
M. Aravagiri et al., "PLASMA-CONCENTRATIONS OF RISPERIDONE AND ITS 9-HYDROXY METABOLITE ANDTHEIR RELATIONSHIP TO DOSE IN SCHIZOPHRENIC-PATIENTS - SIMULTANEOUS DETERMINATION BY A HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH ELECTROCHEMICAL DETECTION", Pharmacopsychiatry, 31(3), 1998, pp. 102-109

Abstract

A simple, sensitive and accurate method for the simultaneous determination of risperidone (RSP) and its 9-hydroxy metabolite (9-OH-RSP) in human plasma is described. The relationship between dose of RSP and the plasma concentration of RSP and 9-OH-RSP in a clinical situation is discussed. Both compounds were isolated from plasma by a simple one-step liquid-liquid extraction with 15% methylene chloride in pentane. High-performance liquid chromatography separations were made on a cyano column and the compounds were detected by electrochemical detector. The method had sufficient sensitivity to determine RSP and 9-OH-RSP accurately at concentrations as low as 0.25 ng/ml when 1 ml of plasma is used for the analysis. The assay determinations were accurate, precise and consistent with a coefficient of variation less than 15%. Commonlyco-administered drugs and other antipsychotics did not interfere withthe analysis of either RSP or 9-OH-RSP There were large variations ininter- and intra-individual values of plasma concentrations of RSP and 9-OH-RSP. The 9-OH-RSP appears to be the major circulating active moiety and its plasma concentrations were, on the average 22 fold higherthan that of RSP in schizophrenic patients treated with RSP. The ratio of RSP/9-OH-RSP concentrations suggested that three of the patients may have deficiency in cytochrome P450 enzyme CYP 2D6. The plasma concentrations of RSP showed a weak relationship with the administered daily oral dose (r = 0.4684, p = 0.01, n = 215). However, there was a good relationship between the daily dose of RSP and the plasma concentration of 9-OH-RSP (r = 0.6654, p = 0.01, n = 280) or the total active moiety, sum of RSP and 9-OH-RSP concentrations (r = 0.7041, p = 0.0005, n = 280). The measurement of the total active moiety in plasma of schizophrenic patients may be useful for assessing the relationship between dose and plasma concentration and dose and clinical outcome of patients rather than measuring RSP alone.

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Documento generato il 26/01/20 alle ore 00:48:09