Psychopharmacology

, Volume 90, Issue 4, pp 468–470

Effects of smoking on haloperidol and reduced haloperidol plasma concentrations and haloperidol clearance

  • Michael W. Jann
  • Stephen R. Saklad
  • Larry Ereshefsky
  • Ann L. Richards
  • Charles A. Harrington
  • Chester M. Davis
Original Investigations

Abstract

Plasma concentrations of haloperidol and its reduced metabolite (reduced haloperidol) were investigated in cigarette smokers (N=23) and nonsmokers (N=27). Steady-state plasma concentrations were obtained 12 h post bedtime dose. Haloperidol and reduced haloperidol concentrations were determined by RIA. Reduced haloperidol was separated by selective succinylation and liquid chromatography. Patients were clinically assessed with the Clinical Global Impression Scale (CGIS). Smokers had significantly lower haloperidol and reduced haloperidol plasma concentrations than nonsmokers (P<0.01, P<0.05). Clearance of haloperidol was significantly greater in smokers compared to nonsmokers (P=0.0052). CGIS assessments did not show significant differences between smokers and non-smokers. Plasma concentrations should be carefully monitored when patients either start or stop smoking.

Key words

Smoking Haloperidol Reduced haloperidol Plasma concentrations Clearance 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Browning JL, Harrington CA, Davis CM (1985) Quantification of reduced haloperidol and haloperidol by radioimmunoassay. J Immunoassay 6:45–66Google Scholar
  2. 2.
    Browning JL, Silverman PB, Harrington CA, Davis CM (1982) Preliminary behavioral and pharmacological studies on the haloperidol metabolite reduced haloperidol. Presented at the Society for Neuroscience 8:470 (abstract)Google Scholar
  3. 3.
    Ereshefsky L, Davis CM, Harrington CA, Jann MW, Browning JL, Saklad SR, Burc NR (1984) Haloperidol and reduced haloperidol plasma levels in selected schizophrenic patients. J Clin Psychopharmacol 4:138–142Google Scholar
  4. 4.
    Ereshefsky L, Jann MW, Saklad SR, Davis CM, Richards AL, Burch NR (1985) Effects of smoking on fluphenazine clearance in psychiatric inpatients. Biol Psychiatry 20:329–332Google Scholar
  5. 5.
    Forsman A, Larsson M (1978) Metabolism of haloperidol. Curr Ther Res 24:567–568Google Scholar
  6. 6.
    Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd ed., New York, Marcel Dekker, pp 321–322Google Scholar
  7. 7.
    Holley FO, Magliozzi JR, Stanski DR, Lombrozo L, Hallister LE (1983) Haloperidol kinetics after oral and intravenous doses. Clin Pharmacol Ther 33:477–484Google Scholar
  8. 8.
    Hollister LE, Kim DY (1982) Intensive treatment with haloperidol of treatment-resistant chronic schizophrenic patients. Am J Psychiatry 139:1466–1468Google Scholar
  9. 9.
    Jann MW, Ereshefsky L, Saklad SR, Richards AL, Davis CM (1984) Haloperidol and reduced haloperidol plasma levels in schizophrenic patients. Drug Intell Clin Pharm 18:507 (abstract)Google Scholar
  10. 10.
    Jusko WJ (1984) Smoking effects in pharmacokinetics. In: Benet LZ, Massoul N, Gambertoglio JG (eds) Pharmacokinetic basis for drug treatment. Raven Press, New York, pp 311–320Google Scholar
  11. 11.
    Kirsch DG, Bigelow LB, Wyatt RJ (1985) The interpretation of plasma haloperidol concentrations. Arch Gen Psychiatry 42:838–839Google Scholar
  12. 12.
    Korpi ER, Wyatt RJ (1984) Reduced haloperidol: Effects on striatal dopamine metabolism and conversion to haloperidol in the rat. Psychopharmacology 83:34–37Google Scholar
  13. 13.
    Korpi ER, Phelps BH, Granger H, Chang W, Linnoila M, Meek JL, Wyatt RJ (1983) Simultaneous determination of haloperidol and its reduced metabolite in serum and plasma by isocratic liquid chromatography with electrochemical detection. Clin Chem 29:624–628Google Scholar
  14. 14.
    Larsson M, Forsman A, Ohman R (1983) A high-performance liquid chromatographic method for the determination of haloperidol and reduced haloperidol in serum. Curr Ther Res 34:999–1008Google Scholar
  15. 15.
    Linnoila M, George L, Guthrie S, Leventhal B (1981) Effect of alcohol consumption and cigarette smoking on antidepressant levels of depressed patients. Am J Psychiatry 138:841–842Google Scholar
  16. 16.
    Miller DD, Hershey LA, Duffy JP, Abernathy DR, Greenblatt DJ (1984) Serum haloperidol concentrations and clinical response in acute psychosis. J Clin Psychopharmacol 4:305–310Google Scholar
  17. 17.
    Norman TR, Burrows GO, Maguire KP (1977) Cigarette smoking and plasma nortriptyline levels. Clin Pharmacol Ther 4:453–456Google Scholar
  18. 18.
    Pantuck EJ, Pantuck CB, Anderson KE, Conney AH, Kappas A (1982) Cigarette smoking and chlorpromazine disposition and actions. Clin Pharmacol Ther 31:533–538Google Scholar
  19. 19.
    Perel JM, Hurwic MJ, Kanzler MB (1975) Pharmacodynamics of imipramine in depressed patients. Psychopharmacol Bull 11:16–18Google Scholar
  20. 20.
    Stimmel GL, Falloon IRH (1983) Chlorpromazine plasma levels, adverse effects, and tobacco smoking: Case report. J Clin Psychiatry 44:420–422Google Scholar
  21. 21.
    Swett C (1974) Drowsiness due to chlorpromazine in relation to cigarette smoking. Arch Gen Psychiatry 31:211–213Google Scholar
  22. 22.
    Vinarova E, Vinar D, Kalvach Z: Smokers need higher doses of neuroleptic drugs. Biol Psychiatry (in press)Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Michael W. Jann
    • 1
    • 2
    • 5
  • Stephen R. Saklad
    • 1
    • 2
    • 3
    • 6
  • Larry Ereshefsky
    • 1
    • 2
    • 3
    • 6
  • Ann L. Richards
    • 1
    • 6
  • Charles A. Harrington
    • 4
  • Chester M. Davis
    • 4
  1. 1.College of PharmacyThe University of Texas at AustinUSA
  2. 2.Department of PharmacologyThe University of Texas Health Science Center at San AntonioUSA
  3. 3.Department of PsychiatryThe University of Texas Health Science Center at San AntonioUSA
  4. 4.Department of PsychiatryUniversity of Texas Mental Science InstituteUSA
  5. 5.San Antonio State SchoolUSA
  6. 6.San Antonio State HospitalSan AntonioUSA
  7. 7.Clinical Pharmacy ProgramThe University of Texas Health Science CenterSan AntonioUSA

Personalised recommendations