The influence of various factors in the in vitro distribution of haloperidol in human blood.

Haloperidol is 89.6+/-0.3% bound (mean+/-s.e. mean) in human plasma under in vitro conditions and the free drug distributes rapidly between the plasma and the cellular elements of blood. The cell/plasma partition ratio was 1.12+/-0.06 (mean+/-s.e. mean). Alteration of plasma binding by dilution with buffer showed that uptake of haloperidol by the cellular elements of blood was proportional to free drug concentration. Bishydroxycoumarin (95 ot 286 mug/ml) reduced plasma binding of haloperidol and the displaced haloperidol was taken up by the cellular blood elements. The experiments indicate that the cellular compartment of blood as well as the plasma compartment may act as a sink for haloperidol and drug displacement interactions should therefore be interpreted with a knowledge of both of these compartments.