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Clinical Pharmacology (Pharmacokinetics)

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Book cover Psychotropic Agents

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 55 / 1))

Abstract

The present chapter describes the pharmacokinetics of antipsychotic drugs in psychiatric patients and normal human volunteers. Special consideration is given to the possible relationship between pharmacokinetic data, particularly plasma levels, and clinical effects.

In the memory of my father Berthold Müller-Oerlinghausen, Sculptor, and my brother-in-law Prof. Gerd Brand, Philosopher, who both died during the final preparation of this manuscript

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References

  • Ackenheil, M., Hippius, H.: Clozapine. In: Psychotherapeutic drugs. Usdin, E., Forrest, I.S. (eds.), Part II, pp. 924–956. New York, Basel: Dekker 1977

    Google Scholar 

  • Ackenheil, M., Brau, H., Burkhart, A., Franke, A., Pacha, W.: Antipsychotic effectiveness in relation to plasma level of clozapine. Arzneim. Forsch./Drug Res. 26, 1156–1158 (1976)

    CAS  Google Scholar 

  • Alfredsson, G., Woge-Helgodt, B., 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)

    PubMed  CAS  Google Scholar 

  • Axelsson, R.: On the pharmacokinetics of thioridazine in psychiatric patients. In: Antipsychotic drugs: Pharmacodynamics and pharmacokinetics. Sedvall, G., et al. (eds.), pp. 353–358. Oxford: Pergamon Press 1975

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Axelsson, S., Jönsson, S., Nordgren, L.: Cerebrospinal fluid levels of chlorpromazine and its metabolites in schizophrenia. Arch. Psychiatr. Nervenkr. 221, 167–170 (1975)

    PubMed  CAS  Google Scholar 

  • Belpaire, F.M., Vanderheeren, F.A., Bogaert, M.G.: Binding of thioridazine and some of its metabolites to human serum protein and human albumin. Arzneim. Forsch./Drug Res. 25, 1969–1971 (1975)

    CAS  Google Scholar 

  • Bergling, R., Mjörndal, T., Oreland, L., Rapp, U., Wold, S.: Plasma levels and clinical effects of thioridazine and thiothixene. J. Clin. Pharmacol. 15, 178–186 (1975)

    PubMed  CAS  Google Scholar 

  • Bickel, M.H.: Binding of chlorpromazine and imipramine to red cells, albumin, lipoproteins and other blood components. J. Pharm. Pharmacol. 27, 733–738 (1976)

    Google Scholar 

  • Breyer, U., Villumsen, K.: Measurement of plasma levels of tricyclic psychoactive drugs and their metabolites by UV reflectance photometry of thin layer chromatograms. Eur. J. Clin. Pharmacol. 9, 457–465 (1976)

    CAS  Google Scholar 

  • Breyer, U., Petruch, F., Gaertner, H.J., Pflug, B.: Dünnschichtchromatographische Bestimmung von Plasmaspiegeln tricyklischer Psychopharmaka. Arzneim. Forsch./Drug Res. 26, 1153(1976)

    CAS  Google Scholar 

  • Brinkschulte, M., Jahns, I., Breyer-Pfaff, U.: A method for measuring plasma protein binding of tricyclic psychoactive drugs at therapeutic levels. 11 th Spring Meeting of the German Pharmacological Society, Mainz 1978

    Google Scholar 

  • Burrell, C.D.: Phenothiazines with piperidine side chains. In: Psychotherapeutic drugs. Usdin, E., Forrest, I.S. (eds.), Part II, pp. 795–826. New York: Dekker 1977

    Google Scholar 

  • Buyze, G., Egberts, P.F.C., Musze, R.G., Poslavsky, A.: Blood levels of thioridazine and some of its metabolites in psychiatric patients. A preliminary report. Psychiatr. Neurol. Neurochir. 76, 229–239 (1973)

    PubMed  CAS  Google Scholar 

  • Carr, C.J.: Metabolic studies on psychoactive drugs. Ann. N.Y. Acad. Sci. 96, 170 (1962)

    PubMed  CAS  Google Scholar 

  • Chan, T.L., Sakalis, G., Gershon, S.: Quantitation of chlorpromazine and its metabolites in human plasma and urine by direct spectrodensitometry of thin-layer chromatograms. In: The phenothiazines and structurally related drugs. Forrest, I.S., Carr, C.J., Usdin, E. (eds.), pp. 323–333. New York: Raven Press 1974

    Google Scholar 

  • Chouinard, G., Annable, L., Cooper, S.: Antiparkinsonian drug administration and plasma levels of penfluridol. A new long-acting neuroleptic. Comm. Psychopharmacol. 1, 325–332 (1977)

    CAS  Google Scholar 

  • Christoph, G.W., Schmidt, D.E., Davis, J.M., Janowsky, D.S.: A method for determination of chlorpromazine in human blood serum. Clin. Chim. Acta 38, 265 (1972)

    PubMed  CAS  Google Scholar 

  • Clark, B.R., Tower, B.B., Rubin, R.T.: Radioimmunoassay of haloperidol in human serum. Life Sci. 20, 319–325 (1977)

    PubMed  CAS  Google Scholar 

  • Clark, M.L., Kaul, P.N.: A preliminary report on clinical response and blood levels of chlorpromazine and its sulfoxide during chlorpromazine therapy in chronic schizophrenic patients. Psychopharmacol. Bull. 11, 28–30 (1975)

    PubMed  CAS  Google Scholar 

  • Clark, M.L., 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: Pharmacokinetics of psychoactive drugs. Gottschalk, L.A., Merlis, S. (eds.), pp. 191–197. New York: Spectrum Publications 1976

    Google Scholar 

  • Cooper, S.F., Albert, J.-M., Hillel, J., Caille, G.: Plasmalevel studies of chlorpromazine following the administration of chlorpromazine hydrochloride and chlorpromazine embonate in chronic schizophrenics. Curr. Ther. Res. 15, 73–77 (1973)

    PubMed  CAS  Google Scholar 

  • Cooper, S.F., Albert, J.-M., Dugal, R., Bertrand, M.: Separation of perphenazine, its sulphoxide and its probable phenolic metabolites by electron-capture gas-liquid chromatography. J. Chromatogr. 150, 263–265 (1978)

    CAS  Google Scholar 

  • Cooper, T.B., Simpson, G.M., Haber, E.J., Bergner, E.-E.E.: Butaperazine pharmacokinetics. Effect of dosage regimen on steady state blood levels. Arch. Gen. Psychiatry 32, 903–905 (1975)

    PubMed  CAS  Google Scholar 

  • Coutselinis, A., Boukis, D., Kentarchou, P.: Haloperidol concentrations in blood in cases of acute intoxication (letter). Clin. Chem. 23, 900 (1977)

    PubMed  CAS  Google Scholar 

  • Cowen, M.A., Martin, W.C.: Long-term chlorpromazine retention and its modification by steroids. Am. J. Psychiatry 125, 243 (1968)

    PubMed  CAS  Google Scholar 

  • Cressman, W.A., Bianchine, J.R., Slotnick, V.B., Johnson, P.C., Plostnieks, J.: Plasma level profile of haloperidol in man following intramuscular administration. Eur. J. Clin. Pharmacol. 7, 99–103 (1974)

    PubMed  CAS  Google Scholar 

  • Curry, S.H.: Method for the estimation of nanogram quantities of chlorpromazine and some of its relatively monopolar metabolites in plasma using gas chromatography with an electron capture detector. Anal. Chem. 40, 1251 (1968)

    PubMed  CAS  Google Scholar 

  • Curry, S.H.: Plasma protein binding of chlorpromazine. J. Pharm. Pharmacol. 22, 193–197 (1972)

    Google Scholar 

  • Curry, S.H.: Metabolism and kinetics of chlorpromazine in relation to effect. In: Antipsychotic Drugs: Pharmacodynamics and Pharmacokinetics. Sedvall, G., Uvnäs, B., Zottermann, Y. (eds.), pp. 343–352. New York: Pergamon Press 1975

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Curry, S.H., Mould, G.H.: Gas chromatographic identification of thioridazine in plasma and method for routine assay of the drug. J. Pharm. Pharmacol. 21, 674–677 (1969)

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Curry, S.H., Davis, J.M., Janowsky, D.S., Marshall, J.H.L.: Factors affecting chlorpromazine plasma levels in psychiatric patients. Arch. Gen. Psychiatry 22, 209 (1970)

    PubMed  CAS  Google Scholar 

  • Curry, S.H., Whelpton, R., Schepper, P.J., de Vranckx, S., Schiff, A.A.: Kinetics of fluphenazine after fluphenazine dihydrochloride, enanthate and decanoate administration to man. Br. J. Clin. Pharmacol. 7, 325–331 (1979)

    PubMed  CAS  Google Scholar 

  • Dahl, S.G., Strandjord, R.E.: Pharmacokinetics of chlorpromazine after single and chronic dosage. Clin. Pharmacol. Ther. 21, 437–448 (1977)

    PubMed  CAS  Google Scholar 

  • Dahl, S.G., Strandjord, R.E., Sigfusson, S.: Pharmacokinetics and relative bioavailability of levomepromazine after repeated administration of tablets and syrup. Eur. J. Clin. Pharmacol. 11, 305–310 (1977)

    PubMed  CAS  Google Scholar 

  • Davis, J.M., Janowsky, D.S., Sekerke, H.J., Manier, H., El-Yousef, M.K.: The pharmacokinetics of butaperazine in serum. Adv. Biochem. Psychopharmacol. 9, 433–443 (1974)

    PubMed  CAS  Google Scholar 

  • Davis, C.M., Meyer, C.J., Fenimore, D.C.: Improved gas chromatographic analysis of chlorpromazine in blood serum. Clin. Chim. Acta 78, 71–77 (1977)

    PubMed  CAS  Google Scholar 

  • Dekirmenjian, H., Javaid, J.I., Duslak, B., Davis, J.M.: Determination of antipsychotic drugs by gas-liquid chromatography with a nitrogen detector using a simple acetylation technique. J. Chromatogr. 160, 291–296 (1978)

    PubMed  CAS  Google Scholar 

  • Dencker, S.J., Johansson, R., Lindberg, D.: Correlation between plasma level and clinical response in manic psychotics given high dose fluphenazine enanthate. Acta Psychiatr. Scand. [Suppl.] 265, 22–23 (1976)

    Google Scholar 

  • Dollery, C.T.: Pharmacokinetics — Master or servant? Eur. J. Clin. Pharmacol. 6, 1 (1973)

    PubMed  CAS  Google Scholar 

  • Efron, D.H., Harris, S.R., Manian, A.A., Gandette, L.G.: Radioassay of chlorpromazine and its metabolites in plasma. Psychopharmacologia 19, 207–223 (1971)

    PubMed  CAS  Google Scholar 

  • Eiduson, S., Geller, E.: The excretion and metabolism of 35S-labelled thioridazine in urine, blood, bile and feces. Biochem. Pharmacol. 12, 1429–1435 (1963)

    PubMed  CAS  Google Scholar 

  • Elfernik, J.G.: The asymmetric distribution of chlorpromazine and its quaternary analogue over the erythrocyte membrane. Biochem. Pharmacol. 26, 2411–2416 (1978)

    Google Scholar 

  • El-Yousef, M.K., Manier, D.H.: Letter: Tricyclic antidepressants and phenothiazines. JAMA 229, 1419 (1974a)

    PubMed  CAS  Google Scholar 

  • El-Yousef, M.K., Manier, D.H.: Letter: Estrogen effects on phenothiazine derivative blood levels. JAMA 228, 827–828 (1974b)

    PubMed  CAS  Google Scholar 

  • El-Yousef, M.K., Manier, D.H.: Letter: The effect of benztropine mesylate on plasma levels of butaperazine maleate. Am. J. Psychiatry 131, 471–472 (1974c)

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Fann, W.F., Davis, J.M., Janowsky, D.S., Sekerke, H.J., Schmidt, D.M.: Chlorpromazine: Effects of antacids on its gastrointestinal absorption. J. Clin. Pharmacol. 13, 388 (1973)

    PubMed  CAS  Google Scholar 

  • Flint, D.R., Ferullo, C.R., Levandovski, P., Hwang, B.: More sensitive gas chromatographic measurement of chlorpromazine in plasma. Clin. Chem. 17, 830–835 (1971)

    PubMed  CAS  Google Scholar 

  • Forrest, I.S., Kanter, S.K., Sperco, J.E., Wechsler, M.B.: A comprehensive determination of thioridazine and its metabolites in urine. Am. J. Psychiatry 121, 1049–1053 (1965)

    PubMed  CAS  Google Scholar 

  • Forrest, I.S., Forrest, F.M., Bolt, A.G., Serra, M.T.: An attempt to correlate urinary chlorpromazine excretion with clinical response to drug therapy. In: Proceedings of the Vth International Congress of Neuropsychopharmacology. Cole, J.O., Deniker, P., Hippius, H., Bradley, P.B. (eds.). Amsterdam: Excerpta Medica 1967

    Google Scholar 

  • Forrest, I.M., Forrest, F.M., Serra, M.T.: Chlorpromazine retention. Am. J. Psychiatry 118, 300–307 (1969)

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Forrest, F.M., Forrest, I.S., Finkle, B.S.: Alcohol-chlorpromazine interaction in psychiatric patients. Agressologie 13, 67–74 (1972)

    PubMed  CAS  Google Scholar 

  • Forsman, A.O.: Individual variability in response to haloperidol. Proc. R. Soc. Med. 69, Suppl. 1, 9–12 (1976)

    PubMed  Google Scholar 

  • Forsman, A., Öhman, R.: Some aspects of the distribution and metabolism of haloperidol in man. In: Antipsychotic drugs: Pharmacodynamics and pharmacokinetics. Sedvall, G., Uvnäs, B., Zotterman, Y. (eds.), pp. 359–365. Oxford, New York, Toronto, Sydney, Paris, Frankfurt: Pergamon Press 1975

    Google Scholar 

  • Forsman, A., Öhman, R.: Studies on serum protein binding of haloperidol. Curr. Ther. Res. 21, 245–255 (1977)

    PubMed  CAS  Google Scholar 

  • Forsman, A., Martensson, E., Nyberg, G., Öhman, R.: A gas chromatographic method for determining haloperidol. A sensitive procedure for studying serum concentration and pharmacokinetics of haloperidol in patients. Naunyn Schmiedeberg’s Arch. Pharmacol. 286, 113–124(1974)

    CAS  Google Scholar 

  • Franklin, M., Wiles, D.H., Harvey, D.J.: Sensitive gas-chromatographic determination of fluphenazine in human plasma. Clin. Chem. 24, 41–44 (1978)

    PubMed  CAS  Google Scholar 

  • Gabay, S., Huang, P.C.: The binding behavior of phenothiazines and structurally related compounds to albumin from several species. In: The phenothiazines and structurally related drugs. Forrest, I.S., Carr, C.J., Usdin, E. (eds.), pp. 175–189. New York: Raven Press 1974

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Garver, D.L., Dekirmenjian, H., Davis, J.M., Casper, R., Ericksen, S.: Neuroleptic drug levels and therapeutic response: preliminary observations with red blood cell-bound butaperazine. Am. J. Psychiatry 134, 304–307 (1977)

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Gottschalk, L.A.: A preliminary approach to the problems of relating the pharmacokinetics of phenothiazines to clinical response with schizophrenic patients. Psychopharmacol. Bull. 14, 35–39 (1978)

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Gottschalk, L.A., Dinovo, E., Biener, R.: Plasma levels of mesoridazine and its metabolites and clinical response in acute schizophrenia after a single intramuscular drug dose. Psychopharmacol. Bull. 11, 33–34 (1975b)

    PubMed  CAS  Google Scholar 

  • Gottschalk, L.A., Dinovo, E., Biener, R., Birch, H., Syben, M., Noble, E.P.: Plasma levels of mesoridazine and its metabolites and clinical response in acute schizophrenia after a single intramuscular drug dose. In: Pharmacokinetics of psychoactive drugs. Gottschalk, L.A., Merlis, S. (eds.), pp. 171–189. New York: Spectrum Publications 1976

    Google Scholar 

  • Gottschalk, L.A., Dinovo, E., Biener, R., Nandi, B.R.: Plasma concentrations of thioridazine metabolites and ECG abnormalities. J. Pharm. Sci. 67, 155–157 (1978)

    PubMed  CAS  Google Scholar 

  • Gruenke, L.D., Craig, J.C., Dinovo, E.: Identification of a metabolite of thioridazine and mesoridazine from human plasma. Res. Commun. Chem. Pathol. Pharmacol. 10, 221–225 (1975)

    PubMed  CAS  Google Scholar 

  • Hammar, C.G., Holmstedt, B.: Mass fragmentography: Identification of chlorpromazine and its metabolites in human blood by a new method. Anal. Biochem. 25, 532–548 (1968)

    PubMed  CAS  Google Scholar 

  • Hansen, C.E., Kragh-Sorensen, P.: Clinical-pharmacological aspects of measuring perphenazine in human blood. Acta Psychiatr. Scand. [Suppl.] 246, 18–22 (1973)

    CAS  Google Scholar 

  • Hansen, C.E., Larsen, N.E.: Perphenazine concentrations in human whole blood. Psychopharmacologia (Bed.) 37, 31–36 (1974)

    CAS  Google Scholar 

  • Hansen, C.E., Christensen, R.T., Elley, J., Hansen, B.L., Kragh-Sørensen, P., Larsen, N.E., Naestoff, J., Hvidberg, E.F.: Clinical pharmacokinetic studies of perphenazine. Br. J. Clin. Pharmacol. 3, 915–923 (1976)

    CAS  Google Scholar 

  • Hansen, L.B., Larsen, N.E.: Plasma concentrations of perphenazine and its sulphoxide metabolite during continuous oral treatment. Psychopharmacology 53, 127–130 (1977)

    PubMed  CAS  Google Scholar 

  • Hollister, L.E., Kanter, S.L., Wright, A.: Comparison of intramuscular and oral administration of chlorpromazine and thioridazine. Arch. Int. Pharmacodyn. Ther. 144, 571–578 (1963)

    PubMed  CAS  Google Scholar 

  • Hollister, L.E., Curry, S.H., Derr, J.E., Kanter, S.L.: Studies of delayed-action medication. V. Plasma levels and urinary excretion of four different dosage forms of chlorpromazine. Clin. Pharmacol. Ther. 11, 49–59 (1970)

    PubMed  CAS  Google Scholar 

  • Huang, C.L., Kurland, A.A.: Chlorpromazine blood level in psychotic patients. Arch. Gen. Psychiatry 5, 509–513(1961)

    PubMed  CAS  Google Scholar 

  • Huang, CL., Ruskin, B.H.: Determination of serum chlorpromazine metabolites in psychiatric patients. J. Nerv. Ment. Dis. 139, 381–386 (1964)

    PubMed  CAS  Google Scholar 

  • Hughes, I.E., Jellett, L.B., Ilett, K.F.: The influence of various factors in the in vitro distribution of haloperidol in human blood. Br. J. Clin. Pharmacol. 3, 285–288 (1976)

    PubMed  CAS  Google Scholar 

  • Jacobsson, I., Knorring, L. von, Mattson, B., Mjörndal, T., Oreland, L., Perris, C, Rapp, W., Edenius, B., Kettner, B., Magnusson, K.E., Villemoes, P.: Penfluridol and thiothixene. Dosage, plasma levels and changes in psychopathology. Int. Pharmacopsychiatry 11, 206–214 (1976)

    PubMed  CAS  Google Scholar 

  • Jähnchen, E., Krieglstein, J., Kuschinsky, G.: Die Bedeutung der Benzolringe bei der Eiweißbindung von Promazin und Chlorpromazin. Naunyn Schmiedeberg’s Arch. Pharmacol. Exp. Pathol. 263, 375–386 (1969)

    Google Scholar 

  • Johansson, R., Borg, K.O., Gabrielsson, M.: Determination of fluphenazine in plasma by ionpair partition chromatography. Acta Pharm. Suec. 13, 193–200 (1976)

    PubMed  CAS  Google Scholar 

  • Jonghe, F.E. de, Helm, H.J. van der: Plasma concentrations of thioridazine in patients with depression. Acta Psychiatr. Scand. 46, 360–364 (1970)

    PubMed  Google Scholar 

  • Jonghe, F.E. de, Helm, H.J. van der, Schalken, H.F., Thiel, J.H.: Therapeutic effect and plasma level of thioridazine. Acta Psychiatr. Scand. 49, 535–545 (1973)

    PubMed  Google Scholar 

  • Jørgensen, A., Gottfries, CG.: Pharmacokinetic studies on flupenthixol and flupenthixol decanoate in man using tritium labelled compounds. Psychopharmacologia 27, 1–10 (1972)

    PubMed  Google Scholar 

  • Jørgensen, A., Hansen, V., Larsen, U.D., Khan, A.R.: Metabolism, distribution and excretion of flupentixol. Acta Pharmacol. Toxicol. 27, 301–313 (1969)

    Google Scholar 

  • Kaul, P.N., Conway, M.W., Ticku, M.K., Clark, M.L.: Chlorpromazine metabolism II: Determination of nonconjugated metabolites in blood of schizophrenic patients. J. Pharm. Sci. 61, 581 (1972)

    PubMed  CAS  Google Scholar 

  • Kaul, P.N., Conway, M.W., Ticku, M.K., Clark, M.L.: Chlorpromazine metabolism. III. Determination of conjugated metabolites in the blood of schizophrenic patients. J. Lab. Clin. Med. 81, 467 (1973)

    PubMed  CAS  Google Scholar 

  • May, P.R.A., Putten, T. van: Plasma levels of chlorpromazine in schizophrenia. Arch. Gen. Psychiatry 35, 1081–1087 (1978)

    PubMed  CAS  Google Scholar 

  • May, P.R.A., Putten, T. van, Jenden, D.J., Cho, A.K.: Test dose response in schizophrenia. Arch. Gen. Psychiatry 35, 1091–1097 (1978)

    PubMed  CAS  Google Scholar 

  • Maxwell, J.D., Carrella, M., Parky, J.D., Williams, R., Mould, G.P., Curry, S.H.: Plasma disappearance and cerebral effects of chlorpromazine in cirrhosis. Clin. Sci. 43, 143–151 (1972)

    PubMed  CAS  Google Scholar 

  • Mellinger, T.J., Mellinger, E.M., Smith, W.T.: Thioridazine blood levels in patients receiving different oral forms. Clin. Pharmacol. Ther. 6, 486–491 (1965)

    PubMed  CAS  Google Scholar 

  • Müller-Oerlinghausen, B.: Bedeutung der Pharmakokinetik für die Therapie mit Antidepressiva. Pharmakopsychiatr. Neuropsychopharmakol. 11, 55–62 (1978)

    PubMed  Google Scholar 

  • Müller-Oerlinghausen, B., Riedel, E., Schley, J.: Thin-layer and gas-liquid chromatographic procedures for the determination of perazine and its metabolites in human body fluids. Int. J. Clin. Pharmacol. 15, 366–372 (1977)

    Google Scholar 

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

    Google Scholar 

  • Muusze, R.G., Vanderheeren, F.A.: Plasma levels and half lives of thioridazine and some of its metabolites. II. Low doses in older psychiatric patients. Eur. J. Clin. Pharmacol. 11, 141–147 (1977)

    PubMed  CAS  Google Scholar 

  • Muusze, R.G., Huber, J.F.K.: Determination of the psychotropic drug thioridazine and its metabolites in blood by means of high pressure liquid chromatography in combination with fluorometric reaction detection. J. Chromatogr. Sci. 12, 779–787 (1974)

    PubMed  CAS  Google Scholar 

  • Neve, H.K.: The excretion of thioridazine (Melleril, TP 21) in urine. Acta Pharmacol. Toxicol. 17, 404–409 (1960)

    CAS  Google Scholar 

  • Nikitopoulou, G., Thorner, M., Crammer, J., Lader, M.: Prolactin and psychophysiologic measures after single doses of thioridazine. Clin. Pharmacol. Ther. 21, 422–429 (1977)

    PubMed  CAS  Google Scholar 

  • Nyberg, G., Axelsson, R., Martensson, E.: Binding of thioridazine and thioridazine metabolites to serum proteins in psychiatric patients. Eur. J. Clin. Pharmacol. 14, 341–350 (1978)

    PubMed  CAS  Google Scholar 

  • Pacha, W.L.: A method for the fluorometric determination of thioridazine or mesoridazine in plasma. Experientia 25, 103–104 (1969)

    PubMed  CAS  Google Scholar 

  • Perel, J.M., Manian, A.A.: Pharmacokinetics of therapeutic and toxic reactions: I. Phenothiazines. Neurotoxicology 1, 9–13 (1977)

    CAS  Google Scholar 

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

    Google Scholar 

  • Pietzcker, A., Müller-Oerlinghausen, B., Schley, J., Chaskel, R., Poppenberg, A., Urban, R.: Beziehungen zwischen Serumkonzentration und klinischen Befunden bei langfristig mit Perazin behandelten schizophrenen Patienten. Arzneim. Forsch./Drug Res. 28, 1302–1303 (1978)

    CAS  Google Scholar 

  • Ragland, J.B., Kinross-Wright, V.J., Ragland, R.: Determinations of phenothiazines in biological samples. Anal. Biochem. 12, 60–69 (1965)

    PubMed  CAS  Google Scholar 

  • Rivera-Calimlim, L., Siracusa, A.: Plasma assay of fluphenazine. Commun. Psychopharmacol. 1, 233–242 (1977)

    PubMed  CAS  Google Scholar 

  • Rivera-Calimlim, L., Castaneda, L., Lasagna, L.: Effects of mode of management on plasma chlorpromazine in psychiatrie patients. Clin. Pharmacol. Ther. 14, 978–981 (1973)

    PubMed  CAS  Google Scholar 

  • Rivera-Calimlim, L., Nasrallah, H., Strauss, J., Lasagna, L.: Clinical response and plasma levels: Effect of dose, dosage schedules, and drug interaction on plasma chlorpromazin levels. Am. J. Psychiatry 133, 646–652 (1976)

    PubMed  CAS  Google Scholar 

  • Rivera-Calimlim, L., Kerzner, B., Karch, F.E.: Effect of lithium on plasma chlorpromazine levels. Clin. Pharmacol. Ther. 23, 451–455 (1978)

    PubMed  CAS  Google Scholar 

  • 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. 13, 931–946 (1972)

    PubMed  CAS  Google Scholar 

  • Sakalis, G., Chan, T.L., Gershon, S., Park, S.: The possible role of metabolites in therapeutic response to chlorpromazine treatment. Psychopharmacologia (Berl.) 32, 279–284 (1973)

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Schley, J., Riedel, E., Müller-Oerlinghausen, B.: Determination of perazine serum levels by gas liquid chromatography under clinical routine conditions. J. Clin. Chem. Clin. Biochem. 16, 307–311 (1978)

    PubMed  CAS  Google Scholar 

  • Schley, J., Nündel, M., Riedel, E., Müller-Oerlinghausen, B.: Eine spezifische Serumproteinbindung des Neuroleptikums Perazin. Arzneim. Forsch./Drug Res. 29, 106–108 (1979)

    CAS  Google Scholar 

  • Schley, J.: Zur spezifischen Bindung des Neuroleptikums Perazin an Serumproteine. Naunyn-Schmiedeberg’s Arch. Pharmacol. 307, (Suppl.) R 70 (1979)

    Google Scholar 

  • Schooler, N.R., Sakalis, G., Chan, T.L.: Chlorpromazine metabolism and clinical response in acute schizophrenia: A preliminary report. Psychopharmacol. Bull. 11, 30–33 (1975)

    PubMed  CAS  Google Scholar 

  • Schooler, N.R., Sakalis, G., Chan, T.L., Gershon, S., Goldberg, S.C., Collins, P.: Chlorpromazine metabolism and clinical response in acute schizophrenia: A preliminary report. In: Pharmacokinetics of psychoactive drugs: Blood levels and clinical response. Gottschalk, L.A., Merlis, S. (eds.), pp. 199–219. New York: Spectrum Publications 1976

    Google Scholar 

  • Sharpies, D.: The binding of chlorpromazine to human serum albumin. J. Pharm. Pharmacol. 26, 640–641 (1975)

    Google Scholar 

  • Simpson, G.M., Cooper, T.A.: Clozapine plasma levels and convulsions. Am. J. Psychiatry 135, 99–100 (1978)

    PubMed  CAS  Google Scholar 

  • Simpson, G.M., Varga, E., Reiss, M. Cooper, T.B., Bergner, E.E., Lee, J.H.: Bioequivalency of generic and brand-named chlorpromazine. Clin. Pharmacol. Ther. 15, 631–641 (1974)

    PubMed  CAS  Google Scholar 

  • Simpson, G.M., Cooper, T.B., Lee, J.H., Young, M.A.: Clinical and plasma level characteristics of intramuscular and oral loxapine. Psychopharmacology 56, 225–232 (1978)

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Smolen, V.F., Murdock, H.R. Jr., Stoltman, W.P., Clevenger, J.W., Combs, L.W., Williams, E.J.: Pharmacological response data for comparative bioavailability studies of chlorpromazine oral dosage forms in humans: I. Pupilometry. J. Clin. Pharmacol. 15, 734–751 (1975 a)

    PubMed  CAS  Google Scholar 

  • Smolen, V.F., Murdock, H.R. Jr., Williams, E.J.: Bioavailability analysis of chlorpromazine in humans from pupilometric data. J. Pharmacol. Exp. Ther. 195, 404–415 (1975 b)

    PubMed  CAS  Google Scholar 

  • Smulevitch, A.B., Minsker, E.I., Mazayeva, N.A., Volkova, R.P., Lukanina, S.K.: The problem of clinical activity of long-acting neuroleptics. Compr. Psychiatry 14, 227–232 (1973)

    PubMed  CAS  Google Scholar 

  • Spector, S.: Development of antibodies to chlorpromazine. In: The phenothiazines and structurally related drugs. Forrest, I.S., Carr, C.J., Usdin, E. (eds.), pp. 363–364. New York: Raven Press 1974

    Google Scholar 

  • Spirtes, M.A.: Artifactual contamination of control serum extracts in gas chromatopraphic analyses for chlorpromazine. Clin. Chem. 18, 317–318 (1972)

    PubMed  CAS  Google Scholar 

  • Sugerman, A.A., Rosen, R.: Absorption efficiency and excretion profile of prolonged-action form of chlorpromazine. Clin. Pharmacol. 5, 561–568 (1964)

    CAS  Google Scholar 

  • Sved, S., Perales, A., Palaic, D.: Chlorpromazine metabolism in chronic schizophrenics. Br. J. Psychiatry 119, 589–596 (1971)

    PubMed  CAS  Google Scholar 

  • Sved, S., Perales, A., Houle, H.-P.: Urinary excretion in drug excretion studies in chronic schizophrenics. Br. J. Psychiatry 120, 219–222 (1972)

    PubMed  CAS  Google Scholar 

  • Swett, C.: Drowsiness due to chlorpromazine in relation to cigarette smoking. Arch. Gen. Psychiatry 31, 211–213 (1974)

    PubMed  Google Scholar 

  • Traficante, L.J., Hine, B., Gershon, S., Sakalis, G.: Chloroquine potentiation of thioridazine effects in rats and drugresistent schizophrenic patients: A preliminary report. Commun. Psychopharmacol. 1, 407–419 (1977)

    PubMed  CAS  Google Scholar 

  • Turano, P., Turner, W.J., Donato, D.: Further studies of chlorpromazine metabolism in schizophrenic men. In: The phenothiazines and structurally related drugs. Forrest, I.S., Carr, C.J., Usdin, E. (eds.), pp. 315–322. New York: Raven Press 1974

    Google Scholar 

  • Turner, W.J., Turano, P., Badzinski, S.: An attempt to establish quality control in determination of plasma chlorpromazine by a multi-laboratory collaboration. In: Pharmacokinetics of psychoactive drugs: Blood levels and clinical response. Gottschalk, L.A., Merlis, S. (eds.), pp. 33–42. New York: Spectrum Publications 1976

    Google Scholar 

  • Usdin, E.: The assay of chlorpromazine and metabolites in blood, urine and other tissues. CRC Crit. Rev. Clin. Lab. Sci. 2, 347–391 (1971)

    PubMed  CAS  Google Scholar 

  • Vanderheeren, F.A., Theunis, D.J.: Gas-liquid chromatographic determination of perazine, thioridazine and thioridazine metabolites in human plasma. J. Chromatogr. 120, 123–128 (1976)

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Viala, A.: Pharmacokinetic profile of perphenazine enanthate. Encéphale 2, 273–282 (1976)

    PubMed  CAS  Google Scholar 

  • Vranckx, C.H.: Pharmacokinetics of flupentixol decanoate. Acta Psychiatr. Belg. 74, 529–532 (1974)

    PubMed  CAS  Google Scholar 

  • Wechsler, M., Wharton, R.N., Tanaka, E., Malitz, S.: Chlorpromazine metabolite pattern in psychotic patients. J. Psychiatr. Res. 5, 327–333 (1967)

    PubMed  CAS  Google Scholar 

  • West, N., Vogel, W.H., Boehme, D.H., Gold, S.: Urinary excretion of chlorpromazine and chlorpromazine sulfoxide in four patients on different days. J. Pharm. Sci. 60, 953–954 (1971)

    PubMed  CAS  Google Scholar 

  • West, N.R., Rosenblum, M.P., Springe, H., Gold, S., Boehme, D.H., Vogel, W.H.: Assay procedures for thioridazine, trifluoperazine, and their sulfoxides and determination of urinary excretion of these compounds in mental patients. J. Pharm. Sci. 63, 417–420 (1974)

    PubMed  CAS  Google Scholar 

  • Whelpton, R., Curry, S.H.: Methods for study of fluphenazine kinetics in man. J. Pharm. Pharmacol. 28, 869–873 (1976)

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Wode-Helgodt, B., Borg, S., Fyrö, B., Sedvall, G.: Clinical effects and drug concentrations in plasma and cerebrospinal fluid in psychotic patients treated with fixed doses of chlorpromazine. Acta Psychiat. Scand. 58, 149–173 (1978)

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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Müller-Oerlinghausen, B. (1980). Clinical Pharmacology (Pharmacokinetics). In: Hoffmeister, F., Stille, G. (eds) Psychotropic Agents. Handbook of Experimental Pharmacology, vol 55 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-67538-6_12

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