Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1991 Dec;32(6):677–684.

Clinical pharmacology of prochlorperazine in healthy young males.

A O Isah 1, M D Rawlins 1, D N Bateman 1
PMCID: PMC1368546  PMID: 1768559

Abstract

1. The pharmacokinetics and pharmacodynamics of prochlorperazine (PCZ) have been studied in healthy young males following single 12.5 mg i.v. and 50 mg oral doses, and during repeated doses (25 mg twice daily) for 14 days. 2. Oral bioavailability was low and an N-desmethyl metabolite was detected. Plasma clearance was high (0.98 1 kg-1 h) and the volume of distribution was large (12.9 1 kg-1) after i.v. dosing. 3. The terminal elimination half-life of PCZ was 9 +/- 1 h and 8 +/- 2 h after i.v. and single oral dosing, respectively. The urinary recoveries of drug and metabolite were low. 4. Accumulation of PCZ and its metabolite occurred following repeated dosing. The half-life at the end of 14 days therapy was 18 +/- 4 h. 5. Postural tachycardia, decreased salivary flow, impaired psychomotor function and a diminished level of arousal were observed after intravenous PCZ. Similar effects, but of lower magnitude were observed after single oral doses. During chronic dosing postural tachycardia and antihistaminic effects were observed, the latter not being observed after single doses. 6. After single intravenous dosing the maximal drug effects occurred 2-4 h after peak plasma drug concentrations for all measures except for plasma prolactin and self-scored restlessness 7. An antagonist action at dopamine (D2), muscarinic-cholinergic and alpha-adrenoceptors is postulated after single doses, with antihistaminic effects during chronic dosing, possibly indicating the presence of an active metabolite.

Full text

PDF
682

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bateman D. N., Chapman P. H., Rawlins M. D. The effects of astemizole on histamine-induced weal and flare. Eur J Clin Pharmacol. 1983;25(4):547–551. doi: 10.1007/BF00542126. [DOI] [PubMed] [Google Scholar]
  2. Bateman D. N., Rawlins M. D., Simpson J. M. Extrapyramidal reactions to prochlorperazine and haloperidol in the United Kingdom. Q J Med. 1986 Jun;59(230):549–556. [PubMed] [Google Scholar]
  3. Curry S. H., Whelpton R., de Schepper P. J., Vranckx S., Schiff A. A. Kinetics of fluphenazine after fluphenazine dihydrochloride, enanthate and decanoate administration to man. Br J Clin Pharmacol. 1979 Apr;7(4):325–331. doi: 10.1111/j.1365-2125.1979.tb00941.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DIMASCIO A., HAVENS L. L., KLERMAN G. L. The psychopharmacology of phenothiazine compounds: a comparative study of the effects of chlorpromazine, promethazine, trifluoperazine, and perphenazine in normal males. II. Results and discussion. J Nerv Ment Dis. 1963 Feb;136:168–186. [PubMed] [Google Scholar]
  5. Dollery C. T., Davies D. S., Draffan G. H., Dargie H. J., Dean C. R., Reid J. L., Clare R. A., Murray S. Clinical pharmacology and pharmacokinetics of clonidine. Clin Pharmacol Ther. 1976 Jan;19(1):11–17. doi: 10.1002/cpt197619111. [DOI] [PubMed] [Google Scholar]
  6. Fowler A., Taylor W., Bateman D. N. Plasma prochlorperazine assay by high-performance liquid chromatography--electrochemistry. J Chromatogr. 1986 Jul 11;380(1):202–205. [PubMed] [Google Scholar]
  7. Garver D. L., Davis J. M., Dekirmenjian H., Jones F. D., Casper R., Haraszti J. Pharmacokinetics of red blood cell phenothiazine and clinical effects. Acute dystonic reactions. Arch Gen Psychiatry. 1976 Jul;33(7):862–866. doi: 10.1001/archpsyc.1976.01770070092011. [DOI] [PubMed] [Google Scholar]
  8. HUANG C. L., KURLAND A. A. PERPHENAZINE (TRILAFON) METABOLISM IN PSYCHOTIC PATIENTS. Arch Gen Psychiatry. 1964 Jun;10:639–646. doi: 10.1001/archpsyc.1964.01720240093010. [DOI] [PubMed] [Google Scholar]
  9. Hals P. A., Hall H., Dahl S. G. Phenothiazine drug metabolites: dopamine D2 receptor, alpha 1- and alpha 2-adrenoceptor binding. Eur J Pharmacol. 1986 Jun 24;125(3):373–381. doi: 10.1016/0014-2999(86)90793-4. [DOI] [PubMed] [Google Scholar]
  10. IDESTROM C. M. Experimental pschologic methods applied in psychopharmacology. Acta Psychiatr Scand. 1960;35:302–313. doi: 10.1111/j.1600-0447.1960.tb07602.x. [DOI] [PubMed] [Google Scholar]
  11. Langer G., Sachar E. J., Halpern F. S., Gruen P. H., Solomon M. The prolactin response to neuroleptic drugs. A test of dopaminergic blockade: neuroendocrine studies in normal men. J Clin Endocrinol Metab. 1977 Nov;45(5):996–1002. doi: 10.1210/jcem-45-5-996. [DOI] [PubMed] [Google Scholar]
  12. Lapierre J., Amin M., Hattangadi S. Prochlorperazine--a review of the literature since 1956. Can Psychiatr Assoc J. 1969 Jun;14(3):267–274. doi: 10.1177/070674376901400307. [DOI] [PubMed] [Google Scholar]
  13. Meltzer H. Y., Fang V. S. The effect of neuroleptics on serum prolactin in schizophrenic patients. Arch Gen Psychiatry. 1976 Mar;33(3):279–286. doi: 10.1001/archpsyc.1976.01770030003001. [DOI] [PubMed] [Google Scholar]
  14. Nakra B. R., Bond A. J., Lader M. H. Comparative psychotropic effects of metoclopramide and prochlorperazine in normal subjects. J Clin Pharmacol. 1975 May-Jun;15(5-6):449–454. doi: 10.1002/j.1552-4604.1975.tb02368.x. [DOI] [PubMed] [Google Scholar]
  15. PEVAROFF S. B., HAMELBERG W., BOSOMWORTH P. P. Circulatory effects of intravenous trimethobenzamide hydrochloride, perphenazine, and prochlorperazine. J Oral Surg Anesth Hosp Dent Serv. 1963 Jan;21:24–29. [PubMed] [Google Scholar]
  16. PHILLIPS B. M., MIYA T. S. Excretion of S35 following administration of s35-prochlorperazine to rats subjected to experimental stress. Proc Soc Exp Biol Med. 1962 Mar;109:576–577. doi: 10.3181/00379727-109-27273. [DOI] [PubMed] [Google Scholar]
  17. Peroutka S. J., U'Prichard D. C., Greenberg D. A., Snyder S. H. Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain. Neuropharmacology. 1977 Sep;16(9):549–556. doi: 10.1016/0028-3908(77)90023-5. [DOI] [PubMed] [Google Scholar]
  18. Richelson E. Neuroleptic affinities for human brain receptors and their use in predicting adverse effects. J Clin Psychiatry. 1984 Aug;45(8):331–336. [PubMed] [Google Scholar]
  19. Rivera J. L., Lal S., Ettigi P., Hontela S., Muller H. F., Friesen H. G. Effect of acute and chronic neuroleptic therapy on serum prolactin levels in men and women of different age groups. Clin Endocrinol (Oxf) 1976 May;5(3):273–282. doi: 10.1111/j.1365-2265.1976.tb01953.x. [DOI] [PubMed] [Google Scholar]
  20. Sakalis G., Curry S. H., Mould G. P., Lader M. H. Physiologic and clinical effects of chlorpromazine and their relationship to plasma level. Clin Pharmacol Ther. 1972 Nov-Dec;13(6):931–946. doi: 10.1002/cpt1972136931. [DOI] [PubMed] [Google Scholar]
  21. Sankey M. G., Holt J. E., Kaye C. M. A simple and sensitive H.P.L.C. method for the assay of prochlorperazine in plasma. Br J Clin Pharmacol. 1982 Apr;13(4):578–580. doi: 10.1111/j.1365-2125.1982.tb01427.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Smolen V. F., Murdock H. R., Jr, Williams E. J. Bioavailability analysis of chlorpromazine in humans from pupilometric data. J Pharmacol Exp Ther. 1975 Dec;195(3):404–415. [PubMed] [Google Scholar]
  23. Taylor W. B., Bateman D. N. Preliminary studies of the pharmacokinetics and pharmacodynamics of prochlorperazine in healthy volunteers. Br J Clin Pharmacol. 1987 Feb;23(2):137–142. doi: 10.1111/j.1365-2125.1987.tb03021.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Turkington R. W. Prolactin secretion in patients treated with various drugs: phenothiazines, tricyclic antidepressants, reserpine, and methyldopa. Arch Intern Med. 1972 Sep;130(3):349–354. [PubMed] [Google Scholar]
  25. Uzan A., Le Fur G., Malgouris C. Are antihistamines sedative via a blockade of brain H1 receptors? J Pharm Pharmacol. 1979 Oct;31(10):701–702. doi: 10.1111/j.2042-7158.1979.tb13632.x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES