Predicting haloperidol occupancy of central dopamine D-2 receptors from plasma levels

Positron emission tomography (PET) is increasingly being used to study dopa mine receptor occupancy and the clinical effects of antipsychotic medicatio n. Dopamine D-2 receptor occupancy has been shown to predict several clinic al effects of antipsychotic medication including therapeutic response, moto r and endocrine side-effects. Plasma levels may be used as a surrogate mark er 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 (%D-2 occupancy=plasma level/ED50 +plasma level, where ED50= 0.40 ng/ml) to predict striatal D-2 occupancy fr om plasma level. Twenty-one patients receiving treatment with low dose halo peridol underwent a C-11-raclopride PET scan to measure D-2 occupancy. The D-2 occupancy levels were accurately predicted by use of the previously gen erated equation with only a small degree of error (3.85% CI 0.45-7.33). Pre dicted and measured D-2 occupancy values correlated closely (Pearson's r=0. 864, P=0.003). The study indicates that reliable prediction of D-2 occupanc y from plasma levels is possible. This provides a potentially useful surrog ate measure of D-2 occupancy for research and possibly clinical practice, a s the routine use of PET to measure occupancy levels is not feasible.