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Titolo:
Plasma concentrations of risperidone and 9-hydroxyrisperidone: Effect of comedication with carbamazepine or valproate
Autore:
Spina, E; Avenoso, A; Facciola, G; Salemi, M; Scordo, MG; Giacobello, T; Madia, AG; Perucca, E;
Indirizzi:
Univ Messina, Policlin Univ, Inst Pharmacol, I-98125 Messina, Italy Univ Messina Messina Italy I-98125 nst Pharmacol, I-98125 Messina, Italy Azienda USL 5, Ctr Mental Hlth, Messina, Italy Azienda USL 5 Messina Italy enda USL 5, Ctr Mental Hlth, Messina, Italy Univ Pavia, Dept Internal Med, Clin Pharmacol Unit, Ctr Mental Hlth, I-27100 Pavia, Italy Univ Pavia Pavia Italy I-27100 it, Ctr Mental Hlth, I-27100 Pavia, Italy
Titolo Testata:
THERAPEUTIC DRUG MONITORING
fascicolo: 4, volume: 22, anno: 2000,
pagine: 481 - 485
SICI:
0163-4356(200008)22:4<481:PCORA9>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYTOCHROMES P450 2D6; SERUM CONCENTRATIONS; MAJOR METABOLITES; DRUG-INTERACTIONS; PHARMACOKINETICS; 3A; CLOZAPINE; UPDATE;
Keywords:
risperidone; 9-hydroxyrisperidone; carbamazepine; valproic acid; drug interaction; CYP3A4;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Spina, E Univ Messina, Policlin Univ, Inst Pharmacol, Via Consolare Valeria, I-98125 Messina, Italy Univ Messina Via Consolare Valeria Messina ItalyI-98125 , Italy
Citazione:
E. Spina et al., "Plasma concentrations of risperidone and 9-hydroxyrisperidone: Effect of comedication with carbamazepine or valproate", THER DRUG M, 22(4), 2000, pp. 481-485

Abstract

To evaluate the pharmacokinetic interaction between risperidone and the mood-stabilizing agents carbamazepine and valproic acid, steady state plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-risperidone) were compared in patients treated with risperidone alone (controls, n = 23) and in patients comedicated matched for sex, age, body weight, and antipsychotic dosage. Plasma concentrations of risperidone and 9-OH-risperidone didnot differ between valproate-comedicated patients and controls. By contrast, the concentrations of both compounds were lower in patients taking carbamazepine, although the difference reached statistical significance only forthe metabolite (p < 0.001). The sum of the concentrations of risperidone and 8-OH-risperidone in patients receiving carbamazepine (median 44 nmol/L) was also significantly lower than in patients receiving valproate (168 nmol/L) and in controls (150 nmol/L), In five patients assessed with and without carbamazepine comedication, dose-normalized plasma risperidone and 9-OH-risperidone concentrations were significantly lower when the patients received combination therapy than when they received risperidone alone. In three patients assessed witt and without valproate, no major changes in the levels of risperidone and its metabolite were observed. These findings demonstrate that carbamazepine markedly decreases the plasma concentrations of risperidone and its active 9-OH-metabolite, probably by inducing CYP3A4-mediatedmetabolism. This interaction is likely to be clinically significant. Conversely, valproic acid does not cause any major change in plasma antipsychotic levels.

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Documento generato il 18/01/20 alle ore 10:44:25