Clinical significance of plasma chlorpromazine levels I. Plasma levels of the drug, some of its metabolites and prolactin during acute treatment

Abstract

SynopsisSeventeen acute psychotic patients were studied in the course of chlorpromazine (CPZ) treatment. Blood samples were taken weekly both before and two hours after the morning CPZ dose. Plasma levels of CPZ, CPZ sulphoxide (CPZSO) monodesmethylated CPZ (NOR1CPZ) and 7-hydroxy CPZ (7OH CPZ) were estimated by gas chromatography. Plasma prolactin, luteinizing hormone, testosterone and oestrogens were measured by radioimmunoassay. Six of the seven patients who showed no clinical improvement had plasma CPZ levels equal to or higher than those of patients who improved. ‘Non-responders’ had a greater proportion of CPZ SO in pre-dosage samples. The occurrence of parkinsonian side effects was associated with a mean plasma CPZ of > 50 ng/ml and a mean plasma prolactin of > 30 ng/ml two hours after dosage. The elevation of prolactin preceded the onset of parkinsonian symptoms by 1–2 weeks. There was a significant positive correlation between mean plasma prolactin and mean plasma CPZ levels. The prolactin response may prove a useful index of the central antidopaminergic effect of neuroleptic drugs.

Plasma Level Monitoring of Antipsychotic Drugs

“…Mackay (197S) points out that in this study it is not clear whether the patients were treated long term or for only a short time, and suggests that if the latter was the case then 7 -hydroxy chlorpromazine may not have reached measurable quantities in the plasma. However, Wiles et al (1976) and Kolakowska et al (1976) using a similar technique to that of Mackay were not able to detect 7-hydroxychlorpromazine in all patients, many of whom were chronic schizophrenics receiving long term phenothiazine treatment (see section 3.1.2). Phillipson et al (1977) utilised the technique of Mackay et al (1974) and was able to quantify 7-hydroxychlorpromazine in all 9 patients studied.…”

“…These investigators suggested then that the subsequent decline in plasma levels of chlorpromazine, despite a fixed dose, was the result of enzyme induction. Wiles et al (1976) studied 17 acute psychotic patients receiving a course of chlorpromazine treatment. Blood samples were collected immediately prior to the morning dose (0 hour) and again 2 hours later.…”

Effect of Long-Term Neuroleptic Treatment on Prolactin and Norepinephrine Levels in Serum of Chronic Schizophrenics: Relations to Psychopathology and Extrapyramidal Symptoms

“…46). During acute neuroleptic treatment, the plasma Prl level has been found to be significantly correlated with the serum levels of neuroleptics (31,51,54), but only within a narrow range as there is a maximal Prl response at low doses of neuroleptics, below the therapeutic range (22,34). Another significant correlation between the potency to release Prl and their antipsycho tic property has been reported (22,33).…”

A controlled trial of prostaglandin E1 precursor in chronic neuroleptic resistant schizophrenic patients

“…Assessments of psychiatric state was made using the Brief Psychiatric Rating Scale (BPRS, Overall and Gorham 1962), with the modified glossary employed by Wiles et al (1976) where the item for disorientation item is replaced by an item for elation.…”