Predicting haloperidol occupancy of central dopamine D₂ receptors from plasma levels

Abstract 

Positron emission tomography (PET) is increasingly being used to study dopamine receptor occupancy and the clinical effects of antipsychotic medication. Dopamine D₂ receptor occupancy has been shown to predict several clinical effects of antipsychotic medication including therapeutic response, motor and endocrine side-effects. Plasma levels may be used as a surrogate marker for central occupancy if the relationship between these two measures may be accurately described. This study was designed to test the capacity of a previously derived relationship equation (%D₂ occupancy=plasma level/ED₅₀+plasma level, where ED₅₀= 0.40 ng/ml) to predict striatal D₂ occupancy from plasma level. Twenty-one patients receiving treatment with low dose haloperidol underwent a ¹¹C-raclopride PET scan to measure D₂ occupancy. The D₂ occupancy levels were accurately predicted by use of the previously generated equation with only a small degree of error (3.89% CI 0.45–7.33). Predicted and measured D₂ occupancy values correlated closely (Pearson’s r=0.864, P=0.003). The study indicates that reliable prediction of D₂ occupancy from plasma levels is possible. This provides a potentially useful surrogate measure of D₂ occupancy for research and possibly clinical practice, as the routine use of PET to measure occupancy levels is not feasible.