The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: a PET study.
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 (r2 = 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.
Kapur
S
S
Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, Ontario, Canada.
Zipursky
R
R
Roy
P
P
Jones
C
C
Remington
G
G
Reed
K
K
Houle
S
S
D000284:Administration, Oral; D000328:Adult; D001667:Binding, Competitive; D005260:Female; D006220:Haloperidol / Q000097:blood* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D014055:Tomography, Emission-Computed
D017448:Receptors, Dopamine D2; D006220:Haloperidol