[Standard and high doses of haloperidol. Clinical, pharmacokinetic and pharmacodynamic aspects]

The investigation was designed to study plasma drug concentration and prolactin response determined by two different doses of haloperidol, a standard one and four-fold higher the other, and to explore the relationships between clinical effects and pharmacokinetic and physiological variables in psychotic patients. 24 psychotic patients received haloperidol during 40 consecutive days. During the first 10 days they received 0,25 mg/kg b.w. During the next 20 days they were given 1 mg/kg b.w. Finally they received 0,25 mg/kg b.w. during the last ten days. The patients were clinically assessed and plasma haloperidol and prolactin concentrations were determined on days 0, 5, 10, 20, 30 and 40. In the range of dose studied, the use of higher than conventional doses of haloperidol results in an increased concentration in the cellular site of action and in a more complete blockade of central dopamine receptors. Prolactin response was positive correlated with serum haloperidol concentration. Clinical remission was not direct correlated, neither with serum neuroleptic concentration nor with prolactin level. Those patients who reached higher levels of plasmatic neuroleptic and prolactin concentrations were more susceptible to develop severe extrapyramidal side-effects. Pharmacokinetic and pharmacodynamic monitoring of neuroleptic treatment could be useful to identify these patients.