Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-30T15:04:51.358Z Has data issue: false hasContentIssue false

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Anden, N. E. (1972). Dopamine turnover in the corpus striatum and the limbic system after treatment with neuroleptics and anti-acetylocholine drugs. Journal of Pharmacy and Pharmacology 29, 340348.Google Scholar
Beumont, P. S. V., Corker, C. S., Friesen, H. G., Kolakowska, T., Mandelbrote, B. M., Marshall, J., Murray, M. A. F. & Wiles, D. H. (1974). The effects of phenothiazines on endocrine function: II. British Journal of Psychiatry 124, 420430.CrossRefGoogle ScholarPubMed
Bowers, M. B. Jr & Rozitis, A. (1974). The regional differences in homovanilic acid concentrations after acute and chronic administration of antipsychotic drugs. Journal of Pharmacy and Pharmacology 26, 743745.CrossRefGoogle ScholarPubMed
Cooper, S. F., Albert, J. M., Hillel, J. & Caille, G. (1973). Plasma level studies of chlorpromazine following the administration of chlorpromazine hydrochloride and chlorpromazine embonate in chronic schizophrenics. Current Therapeutic Research 15, 7377.Google ScholarPubMed
Curry, S. H. (1968). Determination of nanogram quantities of chlorpromazine and some of its metabolites using gas liquid chromatography with an electron capture detector. Analytical Chemistry 40, 12511255.CrossRefGoogle ScholarPubMed
Curry, S. H. & Marshall, J. H. L. (1968). Plasma levels of chlorpromazine and some of its relatively non-polar metabolites. Life Sciences 7, 917.CrossRefGoogle ScholarPubMed
Curry, S. H., Marshall, J. H. L., Davis, J. M. & Janovsky, D. S. (1970). Chlorpromazine plasma levels and effects. Archives of General Psychiatry 22, 289296.CrossRefGoogle ScholarPubMed
Davidson, J. D., Terry, L. L. & Sjoerdsma, A. S. (1957). Action and metabolism of chlorpromazine sulfoxide in man. Journal of Pharmacy and Experimental Therapeutics 121, 289–12.Google Scholar
Furuyama, S., Mayes, D. M. & Nugent, C. A. (1970). A radioimmunoassay for plasma testosterone. Steroids 16, 415428.CrossRefGoogle ScholarPubMed
Hotchkiss, J., Atkinson, L. E. & Knobil, E. (1971). Time course of serum oestrogen and luteinizing hormone concentrations during the menstrual cycle of the rhesus monkey. Endocrinology 89, 177183.CrossRefGoogle ScholarPubMed
Kolakowska, T., Wiles, D. H., McNeilly, A. S. & Gelder, M. (1975). Correlation between plasma levels of prolactin and chlorpromazine. Psychological Medicine 5, 214216.CrossRefGoogle ScholarPubMed
Mackay, A. V. P., Healey, A. F. & Baker, J. (1974). The relationship of plasma chlorpromazine to its 7-hydroxy and sulphoxide metabolites in a large population of chronic schizophrenics. British Journal of Clinical Pharmacology 1, 425430.CrossRefGoogle Scholar
McNeilly, A. S. & Hagen, C. (1974). Prolactin, TSH, LH and FSH responses to a combined LHRH/TRH test at different stages of the menstrual cycle. Clinical Endocrinology 3, 427435.CrossRefGoogle ScholarPubMed
March, J. E., Donato, D., Turano, P. & Turner, W. J. (1972). Interpatient variation and significance of plasma levels of chlorpromazine in psychotic patients. Journal of Medicine (Basel3, 146162.Google ScholarPubMed
Martensson, E. & Roos, B. E. (1973). Serum levels of thioridazine in psychiatric patients and healthy volunteers. European Journal of Clinical Pharmacology 6, 181186.CrossRefGoogle ScholarPubMed
Midgley, A. R. (1966). Radioimmunoassay: a method for human chorionic gonadotrophin and human luteinizing hormone. Endocrinology 79, 1018.CrossRefGoogle ScholarPubMed
Overall, G. E. & Gorham, D. R. (1962). The brief psychiatric rating scale. Psychological Reports 10, 799.CrossRefGoogle Scholar
Rivera-Calimlin, L., Castaneda, L. & Lasagna, L. (1973). Effects of mode of management on plasma chlorpromazine in psychiatric patients. Clinical Pharmacology and Therapeutics 979985.Google Scholar
Sakalis, G., Curry, S. H., Mould, G. P. & Lader, M. H. (1972). Physiologic and clinical effects of chlorpromazine and their relationship to plasma level. Clinical Pharmacology and Therapeutics 13, 931946.CrossRefGoogle ScholarPubMed
Sakalis, G., Chan, T. L., Gershon, S. & Park, S. (1973). The possible role of metabolites in therapeutic response to chlorpromazine treatment. Psychopharmacologia (Berlin) 32, 279284.CrossRefGoogle ScholarPubMed
Stephens, J. H., Astrup, Ch. & Mangrum, S. C. (1966). Prognostic factors in recovered and deteriorated schizophrenics. American Journal of Psychiatry 120, 11161121.CrossRefGoogle Scholar
Stevens, J. R. (1973). An anatomy of schizophrenia. Archives of General Psychiatry 29, 177189.CrossRefGoogle ScholarPubMed
Turano, P., March, J. E., Turner, W. J. & Merlis, S. (1972). Qualitative and quantitative report on chlorpromazine and metabolites in plasma, erythocytes and erythrocyte washings from chronically medicated schizophrenic patients. Journal of Medicine (Basel) 3, 109120.Google Scholar
Turner, W. J., Turano, P., Badzinski, S., Breyer, U., Curry, S., Kaul, P. & Wiles, D. (1975). An attempt to establish quality control in determination of plasma chlorpromazine by a multi-laboratory collaboration. In Pharmacokinetics, Blood Levels and Clinical Response of Psychoactive Drugs (ed. Gottschalk, L. & Merlis, S.). Spectrum: New York.Google Scholar