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Psychopharmacology

, Volume 131, Issue 2, pp 148–152 | Cite as

The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: a PET study

  • Shitij Kapur
  • Robert Zipursky
  • Paul Roy
  • Corey Jones
  • Gary Remington
  • Ken Reed
  • Sylvain Houle
ORIGINAL INVESTIGATION

Abstract

The purpose of this study was to determine the relationship between dopamine D2 receptor occupancy and plasma haloperidol. Twelve patients treated with 1–5 mg/day of haloperidol had their D2 occupancy measured using [11C]-raclopride and positron emission tomography and haloperidol plasma levels measured using gas chromatograph mass spectrophotometer. The patients exhibited haloperidol plasma levels ranging from 0.5 to 5.8 ng/ml and D2 occupancy from 53 to 88%. The D2 occupancy was related to the plasma level as a saturating rectangular hyperbola relationship (r 2 = 0.84) and it showed that, on average, 50% D2 occupancy was achieved with 0.51 ng/ml and 80% D2 occupancy with 2.0 ng/ml. Our findings demonstrate that 2–5 mg/day of haloperidol, which usually leads to plasma levels of 1–2 ng/ml, would be expected to induce 60–80% dopamine D2 receptor occupancy. If, as has been claimed, 70% D2 occupancy is adequate for typical neuroleptic response, then the conventional use of >10 mg/day may have been too high, since 70% occupancy can be achieved in most patients by 2–5 mg/day. On the other hand, if as others have suggested, 8–12 ng/ml of haloperidol is the correct therapeutic window for plasma levels, then the required therapeutic D2 occupancy is closer to 90%, not 70%. The implications of the D2 occupancy findings for the optimal dosing of neuroleptics are discussed.

Key words Haloperidol Plasma levels Dopamine D2 receptor Receptor occupancy [11C]-Raclopride Positron Emission Tomography (PET) 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Shitij Kapur
    • 1
  • Robert Zipursky
    • 1
  • Paul Roy
    • 1
  • Corey Jones
    • 2
  • Gary Remington
    • 1
  • Ken Reed
    • 3
  • Sylvain Houle
    • 2
  1. 1.Schizophrenia Research Program, Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8 CA
  2. 2.PET Centre, Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8CA
  3. 3.Queen Street Mental Health Centre, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8CA

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