Skip to main content
Log in

Plasma Level Monitoring of Antipsychotic Drugs

  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Psychotic patients treated with identical doses of antipsychotic drugs have been shown to have great interindividual differences in their steady state plasma concentration. Therefore, monitoring treatment by dosage adjustment alone is of little value. If antipsychotic blood levels can be related to clinical response then their routine measurement may well result in well defined guidelines to individualised optimal dosage.

Despite the considerable effort expended in this field and the many interesting testable hypotheses generated, little substantive evidence for an acceptable plasma level monitoring guide has been reported to date. Work on metabolite level profiles, intra- and extracellular drug concentration differences, more detailed clinical rating scales, and improved experimental design, all show great promise for the future. Investigation of the pharmacokinetics and the elucidation of the often complex metabolic pathways of individual antipsychotic drugs are generating the data base required for the rational pharmacotherapy of these most severely ill patients.

Until more data are available, routine monitoring of antipsychotic drug plasma levels remains of research interest.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Airoldi, L.; Marcucci, F.; Mussini, E. and Garattini, S.: Distribution of penfluridol in rats and mice. European Journal of Pharmacology 25: 291–295 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Alfredsson, G. and Sedval, G.: Mass fragmentographic analysis of chlorpromazine in human plasma; in Sedval, Uvnas and Zotterman (Eds) Antipsychotic Drugs; Pharmacodynamics and Pharmacokinetics, pp. 367–372 (Pergamon Press, Oxford 1976).

    Google Scholar 

  • Alfredsson, G.; Wode-Helgodt, B. and Sedvall, G.; A mass fragmentographic method for the determination of chlorpromazine and two of its active metabolites in human plasma and CSF. Psychopharmacology 48: 123–131 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Alexanderson, B.; Evans, D.A. and Sjoqvist, F.: Steady-state plasma levels of nortriptyline in twins: Influence of genetic factors and drug therapy. British Medical Journal 4: 764–768 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Axelsson, R.: On the pharmacokinetics of thioridazine in psychiatric patients; in Sedvall, Uvnas and Zotterman (Eds) Antipsychotic Drugs; Pharmacodynamics and Pharmacokinetics, pp.353–358 (Pergamon Press. Oxford 1976).

    Google Scholar 

  • Axelsson, R. and Martensson, E.: Serum concentration and elimination from serum of thioridazine in psychiatric patients. Current Therapeutic Research 19: 242–265 (1976).

    PubMed  CAS  Google Scholar 

  • Axelsson. R.: On the serum concentration and antipsychotic effect of thioridazine, thioridazine side chain sulfoxide and thioridazine side chain sulfone, in chronic psychotic patients. Current Therapeutic Research 21: 587–605 (1977).

    Google Scholar 

  • Axelsson, R. and Martensson, E.: The concentration pattern of nonconjugated thioridazine metabolites in serum by thioridazine treatment and its relationship to physiological and clinical variables. Current Therapeutic Research 21: 561–586 (1977).

    CAS  Google Scholar 

  • Belpaire, F.M.; Vanderheeren, F.A.J. and Bogaert, M.G.: Binding of thioridazine and some of its metabolites to human serum protein and human albumin. Arzneimittel-Forschung. 25: 1969–1971 (1975).

    PubMed  CAS  Google Scholar 

  • Bergling, R.; Mjorndal, T.; Oreland, L.; Rapp, W. and Wold, S.: Plasma levels and clinical effects of thioridazine and thiothixene. Journal of Clinical Pharmacology 15: 178–186 (1975).

    PubMed  CAS  Google Scholar 

  • Brodie, B.B.: Distribution and fate of drugs; in Binns(Ed) Absorption and Distribution of Drugs, pp. 199–251 (Livingstone, Edinburgh (1964).

    Google Scholar 

  • Brown, G.A.; Boos, G.I. and Soudijn, W.: Distribution, excretion and metabolism of neuroleptics of the butyrophenone type. Part II. Distribution, excretion and metabolism of haloperidol in Sprague-Dawley rats. European Journal of Pharmacology 1:58 (1967).

    Article  Google Scholar 

  • Bruce, R.B.; Turnbull, L.B.; Newman, J.H., Kinze, J.M.; Morris, P.H. and Pinchbeck, F.M.: Butaperazine dimaleate metabolism. Xenobiotica 4: 197–207 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Buyze, G.; Egberts, P.F.C.; Muusze R.G. and Poslavsky, A.: Blood levels of thioridazine and some of its metabolites in psychiatric patients. A preliminary report. Psychiatrica Neurologica Neurochemica 76: 229–239 (1973).

    CAS  Google Scholar 

  • Chan, T.L. and Gershon, S.: Chlorpromazine Metabolism in Humans. Part I. Quantitation of chlorpromazine and its metabolites in human plasma and urine by direct scan spectrodensitometry. Mikrochimica Acta 3: 435–452 (1973).

    Article  PubMed  Google Scholar 

  • Chan, T.L.; Sakalis, G. and Gershon, S.: Quantitation of chlorpromazine and its metabolites in human plasma and urine by direct spectrodensitometry of thin-layer chromatograms; in Forrest, Carr and Usdin (Eds) Advances in Biochemical Psychopharmacology, vol. 9, pp. 323–333 (Raven Press, New York 1974).

    Google Scholar 

  • Chouinard, G.; Annable, L. and Cooper, S.: Anti-parkinsonian drug administration and plasma levels of penfluridol, a new long acting neuroleptic. Communications in Psychopharmacology 1: 325–331 (1977).

    PubMed  CAS  Google Scholar 

  • Christoph, G.W.; Schmidt, D.E.; Davis, J.M. and Janowsky, D.S.: A method for determination of chlorpromazine in human blood serum. Clinica Chimica Acta 38: 265–270 (1972).

    Article  CAS  Google Scholar 

  • Clark, M.L. and Kaul. P.N.: A preliminary report on clinical response and blood levels of chlorpromazine and its sulfoxide during chlorpromazine therapy in chronic schizophrenic patients; in Gottschalk and Merlis (Eds) Pharmacokinetics of Psychoactive Drugs; Blood Levels and Clinical Response, pp.191–197 (Spectrum., New York 1976).

    Google Scholar 

  • Conney, A.H.: Pharmacological implications of microsomal enzyme induction. Pharmacology Reviews 19: 317 (1967).

    CAS  Google Scholar 

  • Cooper. S.F.; Albert, J.M. and Dugal, R.: Gas-liquid Chromatographic determination of penfluridol in plasma. International Pharmacopsychiatry 10: 78–88 (1975).

    PubMed  CAS  Google Scholar 

  • Cooper. T.B.; Simpson. G.M.; Haher, E.J. and Bergner, P.E.: Butaperazine pharmacokinetics. Archives of General Psychiatry 32: 903–905 (1975b).

    Article  PubMed  CAS  Google Scholar 

  • Cooper, T.B.: Simpson, G.M. and Lee, H.: Thymoleptic and neuroleptic drug plasma levels in psychiatry: Current status; in Pfeiffer and Smythies (Eds) International Review of Neurobiology. Vol. 19, pp.269–309 (Academic Press, New York 1976).

    Google Scholar 

  • Curry, S.H. Determination of nanogram quantities of chlorpromazine and some of its metabolites in plasma using gas-iquid chromatography with an electron capture detector. Analytical Chemistry 40: 1251–1255 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Curry. S.H. and Mould. G.P.: Gas Chromatographic identification of thioridazine in plasma, and a method for routine assay of the drug. Journal of Pharmacy and Pharmacology 21: 674–677 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Curry. S.H.; Davis, J.M.; Janowsky. D.S. and Marshall, J.H.L.: Factors affecting chlorpromazine plasma levels in psychiatric patients. Archives of General Psychiatry 22: 209–215 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Curry, S.H.; D’Mello, A. and Mould, G.P.: Destruction of chlorpromazine during absorption in the rat in vivo and in vitro. British Journal of Pharmacology 42: 403–411 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Curry, S.H.: Chlorpromazine analysis by gas chromatography with electron capture detector; in Forrest, Carr and Usdin (Eds) The Phenothiazines and Structurally Related Drugs, pp.335–345 (Raven Press, New York 1974).

    Google Scholar 

  • Curry. S.H. and Evans. S.: Assay of 7-hydroxychlorpromazine, and failure to detect more than small quantities, in plasma of responding schizophrenics. Psychopharmacology Communications 1: 481–490 (1975).

    PubMed  CAS  Google Scholar 

  • Curry. S.H.: Metabolism and kinetics of chlorpromazine in relation to effect; in Sedvall. Uvnas and Zotterman (Eds) Anti-Psychotic Drugs: Pharmacodynamics and Pharmacokinetics. pp.343–352 (Pergamon Press. Oxford 1976a).

    Google Scholar 

  • Curry. S.H.: Gas-chromatographic methods for the study of chlorpromazine and some of its metabolites in human plasma. Psychopharmacology Communications 2: 1–15 (1976b).

    PubMed  CAS  Google Scholar 

  • Dahl. S.G. and Strandjord, RE.: Pharmacokinetics of chlorpromazine after single and chronic dosage. Clinical Pharmacology and Therapeutics 21: 437–447 (1976).

    Google Scholar 

  • Davis. J.M.; Janowsky. D.S.; Sekerke, H.J.; Marier, H. and El-Yousef, M.K.: The pharmacokinetics of butaperazine in serum: in Forrest, Carr and Usdin (Eds) Phenothiazines and Structurally Related Drugs. pp.433–443 (Raven Press, New York 1973).

    Google Scholar 

  • Dejonghe, F.E. and Van der Helm, H.J.: Plasma concentrations of thioridazine in patients with depression. Acta Psychiatrica Scandinavica 46: 360–364 (1970).

    Article  CAS  Google Scholar 

  • Dinovo, E.C.; Gottschalk, L.A.; Noble, E.P. and Biener, R.: Isolation of a possible new metabolite of thioridazine and mesoridazine from human plasma. Research Communications in Chemical Pathology and Pharmacology 7: 489–496 (1974).

    PubMed  CAS  Google Scholar 

  • Dinovo, E.C.; Gottschalk, L.A.; Nandi, B.R. and Geddes, P.D.: GLC analysis of thioridazine, mesoridazine and their metabolites. J. Pharma. Sci. 65: 667–669 (1976).

    Article  CAS  Google Scholar 

  • El-Yousef, M.K. and Manier, D.H.: Letter to Editor. Tricyclic antidepressants and phenothiazines. Journal of the American Medical Association 229: 1449 (1974a).

    Article  Google Scholar 

  • El-Yousef. M.K. and Manier, D.H.: The effect of benztropine mesylate on plasma levels of butaperazine maleate. American Journal of Psychiatry 131: 471–472 (1974b).

    PubMed  CAS  Google Scholar 

  • El-Yousef, M.K. and Manier, D.H.: Effects of conjugated estrogens on plasma butaperazine levels. Psychopharmacologia 39: 39–41 (1974c).

    Article  PubMed  CAS  Google Scholar 

  • Fann, W.E.; Davis. J.M.; Janowsky. D.S.; Sekerke. H.J. and Schmidt. D.M.: Chlorpromazine: Effects of antacids on its gastrointestinal absorption. Journal of Clinical Pharmacology 13: 388–390 (1973).

    PubMed  CAS  Google Scholar 

  • Flint, D.R.; Ferullo, C.R.: Levandoski. P. and Hwane, B.: More sensitive gas-chromatographic measurements of chlorpromazine in plasma. Clinical Chemistry 17: 830 (1971).

    PubMed  CAS  Google Scholar 

  • Forrest, F.M.; Forrest, I.S. and Serra, M.: Modification of chlorpromazine metabolism by some other drugs frequently administered to psychiatric patients. Biological Psychiatry 2: 53–58 (1970).

    PubMed  CAS  Google Scholar 

  • Foreman, A.; Martensson, E.; Nyberg, G. and Ohman, R.: A gas chromatographic method for determining haloperidol. Naunyn-Schmiedibergs Archives of Pharmacology 286: 113–124 (1974).

    Article  Google Scholar 

  • Forsman, A. and Ohman, R.: Pharmacokinetic studies on haloperidol in man. Current Therapeutic Research 20: 319–336 (1976).

    PubMed  CAS  Google Scholar 

  • Forsman, A. and Ohman, R.: Some aspects of the distribution and metabolism of haloperidol in man; in Sedvall, Uvnas and Zotterman (Eds) Proceedings of the International Symposium held in Wenner-Gren Center, Stockholm. Antipsychotic Drugs: Pharmacodynamics and Pharmacokinetics. Wenner-Gren Center, International Symposium Series, vol 25, pp.359–365 (Pergamon Press, New York 1976b).

    Google Scholar 

  • Foreman, A. and Ohman, R.: Applied pharmacokinetics of haloperidol in man. Current Therapeutic Research 21: 396–408 (1977).

    Google Scholar 

  • Foreman, A.; Folsch, G.; Larsson, M. and Ohman, R.: On the metabolism of haloperidol in man. Current Therapeutic Research 21: 606–661 (1977).

    Google Scholar 

  • Friedel. R.O.: Relationship of pharmacological models of bioavailability of chlorpromazine with drug metabolite blood levels. Psychopharmacology Bulletin 12: 63 (1976).

    PubMed  CAS  Google Scholar 

  • Garver, D.L.; Davis, J.M.; Dekirmenjian, H.; Jones. F.D.: Casper, R. and Haraszti, J.: Pharmacokinetics of red blood cell phenothiazine and clinical effects. Archives of General Psychiatry 33: 862–866 (1976a).

    Article  PubMed  CAS  Google Scholar 

  • Garver, D.L.; Davis, J.M.; Dekirmenjian. H.; Ericksen, S.; Gosenfeld, L. and Haraszti, J.: Dystonie reaction following neuroleptics: time course and proposed mechanisms. Psychopharmacology 47: 199–201 (1976b).

    Article  CAS  Google Scholar 

  • Gautier, J.; Jus, A.; Villeneuve, A.; Jus, K.; Peires. P. and Villeneuve, R.: Influence of the antiparkinsonian drugs on the plasma level of neuroleptics. Biological Psychiatry 12: 389–399 (1977).

    PubMed  CAS  Google Scholar 

  • Gottschalk, LA.; Biener, R.; Noble, E.P.; Birch. H.; Wilbert, D.E. and Heiser, J.F.: Thioridazine plasma levels and clinical response. Comprehensive Psychiatry 16: 323–337 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Gottschalk, L.A.; Dinovo, E.; Biener, R.: Birch, H.; Syben. M. and Noble, E.P.: Plasma levels of mesoridazine and its metabolites and clinical response in acute schizophrenia after a single intramuscular drug dose; in Gottschalk and Merlis (Eds) Pharmacokinetics of Psychoactive Drugs Blood Levels and Clinical Response, pp. 171–189 (Spectrum, New York 1976).

    Google Scholar 

  • Gram, L.F. and Fredericson-Overo, K.: Drug interaction: Inhibitory effects of the neuroleptics on metabolism of tricyclic antidepressants in man. Brit. Med. J. 1: 463–465 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Gram. L.F.: Effects of perphenazine on Imipramine metabolism in man. Psychopharmacology Communications. 1: 165–175 (1975).

    PubMed  CAS  Google Scholar 

  • Gram, L.F.: Factors influencing the metabolism of tricyclic antidepressants. Studies on interactions and first pass metabolism. Danish Medical Bulletin 24: 81–89 (1977).

    PubMed  CAS  Google Scholar 

  • Green. D.E.; Forrest. IS.; Forrest. F.M. and Serra, M.T.: Interpatient variation in chlorpromazine metabolism. Experimental Medicine and Surgery 23: 278–287 (1965).

    PubMed  CAS  Google Scholar 

  • Gruenke, L.D. and Craig, C.: Identification of a metabolite of thioridazine and mesoridazine from human plasma. Research Communications in Chemical Pathology and Pharmacology 10: 221–225 (1975).

    PubMed  CAS  Google Scholar 

  • Hammar, C.G.; Holmstedt, B. and Ryhage, R.: Mass fragmentography, identification of chlorpromazine and its metabolites in human blood by a new method. Analytical Biochemistry 25: 533 (1968).

    Article  Google Scholar 

  • Hansen. C.E.; Christiensen, T.R.; Elley. J.; Hansen. L.B.; Kragh-Sorenson. P.; Larsen. N-E.; Naestoft, J. and Hvidberg, E.F.: Clinical Pharmacokinetic studies of perphenazine. British Journal of Clinical Pharmacology 3: 915–923 (1976).

    Article  CAS  Google Scholar 

  • Hansen. C.E. and Larsen. N-E.: Perphenazine concentration in human whole blood. Psychopharmacologia 37: 31–36 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Hobbs. D.C.; Welch. W.M.; Short, M.J.; Moody, W.A. and van der Velde. C.D.: Pharmacokinetics of thiothixene in man. Clinical Pharmacology and Therapeutics 16: 473–478 (1974).

    PubMed  CAS  Google Scholar 

  • Johansson, R.; Borg. K.O. and Gabrielsson, M.: Determination of fluphenazine in plasma by ion-pair partition chromatography. Acta Pharmaceutic Suecica 3: 193–200 (1976).

    Google Scholar 

  • Kane. J.; Rifkin. A.; Quitkin, F. and Klein. D.: Antipsychotic drug blood levels and clinical outcome; in Klein and Gittelman-Klein (Eds) Progress in Psychiatric Drug Treatment, vol. 2, pp. 399–407 (Brunner Mazel, New York 1976).

    Google Scholar 

  • Kaul. P.N.; Conway, M.W.; Clark, M.L. and Huffine, J.: Chlorpromazine metabolism 1. Quantitative fluorometric method for 11 chlorpromazine metabolites. Journal of Pharmaceutical Sciences 59: 1745–1749 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Kaul, P.N.; Conway, M.W.; Ticka, M.K. and Clark, M.: Chlorpromazine metabolism II. Determination of unconjugated metabolites in blood of schizophrenic patients. Journal of Pharmaceutical Sciences 61: 581–585 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Kawashima, K.; Dixon, R. and Spector, S.: Development of radioimmunoassay for chlorpromazine. European Journal of Pharmacology 32: 195–202 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Klein, H.E.; Candra, O. and Matussek, N.: Therapeutische Wirkung and plasmaspiegel von thioridazin (mellaril) bei schizophen patienten. Pharmakopsychiatrie 8: 122–131 (1975).

    Article  CAS  Google Scholar 

  • Klein, D.F. and Davis, J.M.: Diagnosis and Drug Treatment of Psychiatric Disorders (Williams and Wilkins, Baltimore 1969).

    Google Scholar 

  • Kolakowska, T.; Wiles. D.H.; Gilder, M.G. and McNeilly, A.S.: Clinical significance of plasma chlorpromazine levels. Psychopharmacology 49: 101–107 (1976).

    PubMed  CAS  Google Scholar 

  • Larsen, N.-E. and Naestoft, J.: Determination of perphenazine and fluphenazine in whole blood by gas chromatography. Medical Laboratory Technology 30: 129–132 (1973).

    PubMed  CAS  Google Scholar 

  • Lee, J.H.; Cooper, T.B.; Shrivastava, R.K. and Simpson, G.M.: A study of butaperazine plasma levels with and without antiparkinsonian agent. Submitted for publication (1977).

  • Lehr, R. and Kaul, P.N.: Chlorpromazine metabolism IV: Quaternization as a key to determination of picomoles of chlorpromazine and other tertiary amine drugs. Journal of Pharmaceutical Sciences 64: 950–956 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Loga, S.; Curry, S. and Lader, M.: Interaction of orphenadrine and phenobarbitone with chlorpromazine plasma concentrations and effects in man. British Journal of Clinical Pharmacology 2: 197–208 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Mackay, A.V.P.; Healey, A.F. and Baxter, J.: 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: 425–430 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Mackay, A. V.P.: Comment on paper by Curry and Evans; in Psychopharmacology Communications 1: 491–492 (1975).

    Google Scholar 

  • McQueen, E.D.: Pharmacological basis of adverse drug reactions; in Avery (Ed) Drug Treatment, pp. 161–192 (ADIS Press, Sydney; Churchill Livingstone, Edinburgh; Lea and Febiger, Philadelphia 1976).

    Google Scholar 

  • Manian, A.; Piette, LH.; Holland, D.; Grover, T. and Leterrier, F.: Red blood cell drug binding as a possible mechanism for tranquilization; in Forrest, Carr and Usdin (Eds) The Phenothiazines and Structurally Related Drugs, pp. 149–161 (Raven Press, New York 1974).

    Google Scholar 

  • Manier, D.H.; Sekerte, H.J.; Dingell, J.V. and El-Yousef, M.K.; A fluorometric method for butaperazine in human plasma. Clinica Chimica Acta 57: 225–230 (1974).

    Article  CAS  Google Scholar 

  • Marcucci, F.; Airoldi, L.; Mussini, E. and Garattini, S.: A method for the gas chromatographic determination of butyrophenones. Journal of Chromatography 59: 174–177 (1971a).

    Article  PubMed  CAS  Google Scholar 

  • Marcucci, F.; Mussini, E.; Airoldi, L.; Fanelli, R.; Frigerio, A.; DeNadai, F.; Blzzi, A.; Rizzo, M.; Morselli, P.L. and Garattini. S.: Analytical and pharmacokinetic studies on butyrophenones. Clinica Chimica Acta 34: 321–332 (1971b).

    Article  CAS  Google Scholar 

  • Martensson, E. and Roos, B.-E.: Serum levels of thioridazine in psychiatric patients and healthy volunteers. European Journal of Clinical Pharmacology 6: 181–186 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Martin. E.A.: Etude de la fluorescence des derives de la phenothiazine. Canadian Journal of Chemistry 44: 1783 (1966).

    Article  CAS  Google Scholar 

  • May, P.R.A. and Van Putten, T.: Plasma and saliva levels of chlorpromazine in schizophrenia. A critical review of the literature. Manuscript (1977).

  • Mellinger, T.J. and Keeler, C.E.: Factors influencing spectrofluorometry of phenothiazine drugs. Analytical Chemistry 36: 1840 (1964).

    Article  CAS  Google Scholar 

  • Mjorndal,T. and Oreland, L.: Determination of thioxanthenes in plasma at therapeutic concentrations. Acta Pharmacologica Toxicologica 29: 295–302 (1971).

    Article  CAS  Google Scholar 

  • Muusze, R.G.: Analysis of thioridazine and some of its metabolites in blood by liquid chromatography. Thesis, Amsterdam (1975).

  • Muusze, R.G. and Vanderheeren, F.A.J.: Plasma levels and half lives.II. Low doses in older psychiatric patients. European Journal of Clinical Pharmacology 11: 141–147 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Ng, C.H. and Crammer, J.L.: Measurement of thioridazine in blood and urine. British Journal of Clinical Pharmacology 4: 173–183 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Oliver-Martin, R.; Marzin, D.; Buschenschutz, E.; Pichot, P. and Boissier, J.: Concentrations plasmatiques de l’imipramine et de la desmethylimpramine et effect antidepresseur au cours d’un traitement controle. Psychopharmacologia 14: 187–195 (1975).

    Article  Google Scholar 

  • Pacha, W.L.: A method for the fluorimetric determination of thioridazine (Mellaril) or mesoridazine (Lidanil) in plasma. Ex-perientia 25: 103–104 (1969).

    CAS  Google Scholar 

  • Phillipson. O.T.; McKeown, J.M.; Baker, J. and Healey, A.F.: Correlation between plasma chlorpromazine and its metabolites and clinical ratings in patients with acute relapse of schizophrenic and paranoid psychosis. British Journal of Psychiatry 131: 172–184 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Price-Evans, D.A.: Genetic aspects of drug metabolism; in Cerletti and Bove (Eds) The Present Status of Psychotropic Drugs, p. 111–117 (Excerpta Medica, Amsterdam 1969).

    Google Scholar 

  • Ragland, J.B.; Kinross-Wright, V.J. and Ragland, R.: Determination of phenothiazines in biological samples. Analytical Biochemistry 12: 60–69 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Rivera-Calimlim, L.; Castaneda, L. and Lasagna, L.: Effect of mode of management on plasma chlorpromazine in psychiatric patients. Clinical Pharmacology and Therapeutics 14: 978–986 (1973).

    PubMed  CAS  Google Scholar 

  • Rivera-Calimlim, L.: Effect of lithium on gastric emptying and absorption of oral chlorpromazine. Psychopharmacology Communications 2: 263–272 (1976).

    PubMed  CAS  Google Scholar 

  • Rivera-Calimlim, L.; Masrallah, H.; Strass. J. and Lasagna, L.: Clinical response and plasma levels: effect of dose, dosage schedules, and drug interactions on plasma chlorpromazine levels. American Journal of Psychiatry 133: 646–652, (1976).

    PubMed  CAS  Google Scholar 

  • Sakalis. G.; Curry, S.H.; Mould, G.P. and Lader, M.H.: Physiologic and clinical effects of chlorpromazine and their relationship to plasma level. Clinical Pharmacology and Therapeutics 13: 931–946 (1972).

    PubMed  CAS  Google Scholar 

  • Sakalis, G.; Chan. T.; Gershon, S. and Park, S.: The possible role of metabolites in therapeutic response to chlorpromazine treatment. Psychopharmacologia 32: 284–297 (1973).

    Article  Google Scholar 

  • Sakalis. G.; Chan, T.L.; Sathananthan, G.; Schooler, N.; Goldberg, S. and Gershon, S.: Relationships among clinical response, extrapyramidal syndrome and plasma chlorpromazine and metabolite ratios. Communications in Psychopharmacology 1: 157–166 (1977).

    PubMed  CAS  Google Scholar 

  • Sakurai, Y.; Makahara, T. and Takahashi, R.: Prediction of response of chlorpromazine treatment in schizophrenics. Psychopharmacologia 44: 195–203 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Simpson, G.M.; Cooper, T.B.; Bark, N.; Sud, I. and Lee, J.H.: An investigation of the effect of antiparkinson medication on the plasma level of chlorpromazine. Submitted for publication (1977).

  • Simpson, G.M.; Lament, R.; Cooper, T.B.; Lee, J.H. and Bruce, R.B.: The relationship between blood levels of different forms of butaperazine and clinical response. Journal of Clinical Pharmacology 13: 288–297 (1973).

    PubMed  CAS  Google Scholar 

  • Schooler. N.B.; Sakalis, G.; Chan, T.L.; Gershon, S.; Goldberg, S.C. and Collins, P.: Chlorpromazine metabolism and clinical response in acute schizophrenia: A preliminary report; in Gottschalk and Merlis (Eds) Pharmacokinetics of Psychoactive Drugs: Blood Levels and Clinical Response pp. 199–219 (Spectrum, New York 1976).

    Google Scholar 

  • Soudijn, W.; Van Wijngaarden, J. and Allewijn, F.: Distribution, excretion and metabolism of neuroleptics of the butyrophenone type. Part 1. Excretion and metabolism of haloperidol and nine related butyrophenone-derivatives in the Wistar rat. European Journal of Pharmacology 1: 47 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Smith, R.C.; Dekirmenjian, J.; Davis, J.M.; Crayton, J. and Evans, J.: Plasma butaperazine levels in long-term chronic non-responding schizophrenics. Communications in Psychopharmacology 1: 319–324 (1977).

    PubMed  CAS  Google Scholar 

  • Stevenson. I.N. and Schiff, A.A.: The effect of fluphenazine on steady-state plasma levels of nortriptyline. Letter to Editor. British Journal of Clinical Pharmacology 1: 337–338 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Tjaden, C.R.; Lankelma, J. and Poppe, H.: Anodic coulometric detection with a glassy carbon electrode in combination with reversed-phase high-performance liquid chromatography. Determination of perphenazine and fluphenazine. Journal of Chromatography 125: 275–286 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Turner. W.J.; Turano, P. and Badzinski, S.: An attempt to establish quality control in determination of plasma chlorpromazine by a multi-laboratory collaboration; in Gottschalk and Merlis (Eds) Pharmacokinetics of Psychoactive Drugs: Blood Levels and Clinical Response pp.33–43 (Spectrum, New York 1976)

    Google Scholar 

  • Usdin, E.: The assay of chlorpromazine and metabolites in blood, urine and other tissues. Critical Reviews in Clinical Laboratory Sciences 2: 347–391 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Vanderheeren, F.A.J. and Muusze, R.G.: Plasma levels and half lives of thioridazine and some of its metabolites. I. High doses in young acute schizophrenics. European Journal of Clinical Pharmacology 11: 135–140 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Viukari, N.M. and Salmimies, P.: Serum thioridazine levels after different dosage forms. Lancet 2: 1271 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Whelpton, R. and Curry, S.H.: Gas-chromatographic separation of chlorpromazine, diazepam and N-desmethyldiazepam. Journal of Pharmacy and Pharmacology 27: 970 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Wiles. D.H.; Kolakowska, T.; McNeilly, A.S.; Mandelbrote. B.M. and Gelder, M.G.: Clinical significance of plasma chlorpromazine levels. I. Plasma levels of the drug, some of its metabolites and prolactin during acute treatment. Psychological Medicine 6: 407–415 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Zingales, I.A.: Detection of chlorpromazine and thioridazine metabolites in human erythrocytes. Journal of Chromatography 44: 547–562 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Zingales, I.A.: A gas chromatographic method for the determination of haloperidol in human plasma. Journal of Chromatography 54: 15–24 (1971).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cooper, T.B. Plasma Level Monitoring of Antipsychotic Drugs. Clin Pharmacokinet 3, 14–38 (1978). https://doi.org/10.2165/00003088-197803010-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-197803010-00002

Keywords

Navigation