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

• Published in: Psychopharmacologia Vol. 131; no. 2; pp. 148 - 152
• Main Authors: KAPUR, S, ZIPURSKY, R, ROY, P, JONES, C, REMINGTON, G, REED, K, HOULE, S
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.05.1997
• Subjects: Administration, Oral; Adult; Binding, Competitive; Biological and medical sciences; Female; Haloperidol - blood; Haloperidol - pharmacology; Humans; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptors, Dopamine D2 - drug effects; Tomography, Emission-Computed; Human; Pharmacokinetic pharmacodynamic relationship; Neuroleptic; Psychotropic; Oral administration; Schizophrenia; Butyrophenone derivatives; Haloperidol; Psychosis; Chemotherapy; D2 Dopamine receptor; Treatment; Tomography; Affinity; Antagonist; Mechanism of action; Pharmacokinetics; Positron; Emission tomography
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130050277

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.