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

Published online by Cambridge University Press:  09 July 2009

D. H. Wiles
Affiliation:
University of Oxford, Department of Psychiatry Research Unit, Littlemore Hospital, Oxford, Department of Chemical Pathology, St Bartholomew's Hospital, London
T. Kolakowska
Affiliation:
University of Oxford, Department of Psychiatry Research Unit, Littlemore Hospital, Oxford, Department of Chemical Pathology, St Bartholomew's Hospital, London
A. S. McNeilly
Affiliation:
University of Oxford, Department of Psychiatry Research Unit, Littlemore Hospital, Oxford, Department of Chemical Pathology, St Bartholomew's Hospital, London
B. M. Mandelbrote
Affiliation:
University of Oxford, Department of Psychiatry Research Unit, Littlemore Hospital, Oxford, Department of Chemical Pathology, St Bartholomew's Hospital, London
M. G. Gelder*
Affiliation:
University of Oxford, Department of Psychiatry Research Unit, Littlemore Hospital, Oxford, Department of Chemical Pathology, St Bartholomew's Hospital, London
*
1Address for correspondence: Professor M. G. Gelder, University of Oxford Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX

Synopsis

Seventeen 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.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1976

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