Chlorpromazine In Plasma Research Articles

Radioimmunoassay for chlorpromazine in plasma.

A radioimmunoassay for chlorpromazine in plasma is described. The antiserum was obtained by immunizing rabbits with a conjugate of bovine serum albumin and N-(2-carboxyethyl)desmethylchlorpromazine. It is specific for chlorpromazine and its minor active metabolite, N-desmethylchlorpromazine. Other known active or inactive chlorpromazine metabolites and other psychotropic drugs tested do not cross react with the antiserum. Less than 34 pg of the drug can be detected in 200 muL of plasma. As many as 100 samples can be processed in a day by one technician. Concentrations of chlorpromazine can be measured in 200-muL samples of plasma collected as late as 48 h after a single oral 25-mg dose.

Determination of drugs in plasma by high-performance thin-layer chromatography.

High-performance thin-layer chromatography was used to determine chlorpromazine, amitriptyline, nortriptyline, imipramine, desipramine, phenobarbital, and phenytoin in plasma, to demonstrate the utility of this technique for routine analysis. We quantitated the separated components by use of ultraviolet reflectance spectrometry with detection limits as low as 1 microgram/liter. Regressions of psychoactive agents extracted from plasma were linear over the range of 0 to 300 microgram/liter. The anti-convulsant drugs, phenobarbital and phenytoin, were determined over a range of 0 to 50 mg/liter. Analyses were rapid, reproducible, and well-suited to large-scale programs. Separated components also can be identified in situ by ultraviolet spectrophotometry.

GLC determination of methotrimeprazine and its sulfoxide in plasma.

A GLC method, based on flame-ionization detection, was developed for the assay of methotrimeprazine and its sulfoxide in plasma. For a 6-ml aliquot, the sensitivity was 2-3 ng/ml for the unchanged drug and 4-5 ng/ml for the sulfoxide. The coefficient of variation, calculated from duplicate analyses of plasma samples, was 8-15% for concentrations between 10 and 100 ng/ml. Patients treated with orally administered methotrimeprazine had higher plasma levels of the sulfoxide than of unmetabolized drug. The method also was applied to the analysis of promazine and chlorpromazine in patient plasma.

A relation between drug concentrations in brain and striatal homovanillic acid levels in chlorpromazine treated rats

Levels of homovanillic acid in striatum and chlorpromazine in brain and plasma of rats after acute and chronic treatment were determined by mass fragmentography. A significant positive correlation was found between the striatal homovanillic acid level and the chlorpromazine concentration in brain after acute as well as chronic treatment. A significant relation was also obtained between the homovanillic acid level in striatum and the chlorpromazine content of plasma after acute but not chronic treatment. After chronic treatment the drug concentration-effect relationship was significantly displaced to the right which may indicate the development of pharmacodynamic tolerance to the effect of the drug.

Destruction of chlorpromazine during absorption in the rat in vivo and in vitro.

1. Concentrations of total radioactivity in plasma of rats given intravenous and oral (35)S-chlorpromazine, were similar. Concentrations of unchanged drug, however, were lower after oral doses.2. Chlorpromazine circulated in solution through isolated loops of rat intestine was rapidly absorbed by the tissue. Measurements of glucose transport and histological examination indicated that the tissue was intact. In these in vitro experiments some of the chlorpromazine was converted to products, which together with unchanged drug, were partly retained in the intestinal wall and partly transferred to the serosal side of the tissue. Observations at three concentrations supported the hypothesis that transfer of unchanged drug occurred by passive diffusion.3. Conversion of chlorpromazine to metabolites in the intestine in vivo, would account for the differences in concentrations of chlorpromazine and total radio-activity in plasma after oral doses.