S-oxidation of thioridazine to psychoactive metabolites: an oral dose-proportionality study in healthy volunteers.
Drug Metabol Drug Interact
; 6(3-4): 425-37, 1988.
Article
em En
| MEDLINE
| ID: mdl-3271648
ABSTRACT
Thioridazine has two major active metabolites, which are formed from S-oxidation of its 2-methylthio group; the sulphoxide, mesoridazine, and the sulphone, sulforidazine. Dose proportionality of the three compounds was investigated for the first time in 11 males after administration of three single oral doses (25, 50, and 100 mg) of thioridazine hydrochloride separated in each case by two weeks. Based on the plasma concentrations of the three analytes over 72 h following each dose, large intersubject variabilities in such parameters as AUCot and Cmax were observed for each of the three compounds. The relationships between dose and parameters such as AUCot and Cmax for each analyte were described by an equation for a straight line (r2 greater than or equal to 0.8). However, the mean apparent distribution and elimination rate constants for thioridazine and mesoridazine and the mean apparent oral clearance for thioridazine decreased significantly with increasing dose, suggesting non-linearity in the elimination of thioridazine at high dose.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psicotrópicos
/
Tioridazina
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Drug Metabol Drug Interact
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
1988
Tipo de documento:
Article
País de afiliação:
Canadá