Predicting haloperidol occupancy of central dopamine D2 receptors from plasma levels

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. Received: 4 February 1999 / Final version: 22 October 1999