A fixed dose study of the plasma concentration and clinical effects of thioridazine and its major metabolites
Abstract
Fifty-three patients in an acute episode or exacerbation of psychosis were given thioridazine 200 or 400 mg daily for 2 weeks. Thioridazine and its active metabolites, mesoridazine and sulforidazine, were estimated in plasma by high performance liquid chromatography (HPLC) and radioreceptor assay (RRA). One week after institution of treatment, plasma concentrations of drug were stable in the morning 12h after dosing. Drug levels varied widely between patients, but in all patients the relative level of thioridazine to mesoridazine was about one half and thioridazine to sulforidazine was about two fold. Estimates of neuroleptic activity by RRA and the weighted sum of thioridazine, mesoridazine and sulforidazine by HPLC were very similar. Plasma concentration of parent compound, metabolites, or the sum of active substances as estimated by HPLC or RRA, showed only modest correlations (rs = 0.10-0.22, all NS) to the degree of improvement as measured by change on the Brief Psychiatric Rating Scale. Significant correlations were observed between plasma concentrations of drug and side effects, including dry mouth, blurred vision, or total rating on the Somatic Symptoms Scale. Even patients receiving the lowest dose and achieving the lo...Continue Reading
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