The relationship of plasma chlorpromazine to its 7-hydroxy and sulphoxide metabolites in a large population of chronic schizophrenics.

1 Blood samples were obtained from eighty-six chronic schizophrenics receiving a wide range of oral doses of chlorpromazine. Plasma concentrations of chlorpromazine, 7-hydroxychlorpromazine and chlorpromazine sulphoxide were estimated using a sensitive gas-liquid chromatographic method and their relationships to oral dose and to global clinical control were investigated.2 Wide variability was observed in the plasma concentrations of unchanged drug and metabolites between patients receiving similar daily doses.3 In general the plasma concentrations of the 7-hydroxy and sulphoxide metabolites were of similar magnitude to the concentrations of chlorpromazine.4 Global symptom control was unrelated to the plasma concentration of unchanged chlorpromazine. However, patients judged to be under good control had relatively higher concentrations of the biologically active 7-hydroxy metabolite in their plasma than patients who were poorly controlled and in whom the biologically inactive sulphoxide metabolite predominated. When the ratio of 7-hydroxychlorpromazine to chlorpromazine sulphoxide was derived for each patient, a highly significant difference was found to exist between the metabolite ratios of patients grouped according to clinical control.5 It is suggested that a prediction of therapeutic response to chlorpromazine may be provided in the form of the ratio of the plasma concentration of biologically active metabolite to the concentration of either the unchanged drug or its inactive metabolite.