Monitoring of Serum Haloperidol

Abstract

Haloperidol (Haldol) is a member of the butyrophenone class of neuroleptic drugs used in the treatment of patients with psychotic disorders (for example, schizophrenia). It is also used to control the tics and verbal utterances associated with Gilles de la Tourette's syndrome and to manage intensely hyperexcitable children whose condition does not respond to other treatment modalities. Often, its use is associated with severe toxic side effects, the most serious of which are tardive dyskinesia (which can be irreversible), extrapyramidal reactions with Parkinson-like symptoms, and neuroleptic malignant syndrome. Less serious side effects can include hypotension, anticholinergic effects (blurred vision, dry mouth, constipation, and urinary retention), and sedation, but these effects occur less frequently than with phenothiazine therapy. Although the mechanism of action of haloperidol has not been completely elucidated, its pharmacodynamic activity seems to be related, in part, to its ability to function as a dopamine-receptor antagonist in the central nervous system. Specifically, its effects are thought to be related to the blockage of dopamine receptors in the basal ganglia and limbic regions of the brain.1 Pharmacokinetics.—Substantial interindividual variability is observed in the systemic disposition of haloperidol. Haloperidol is well absorbed from the gastrointestinal tract, but first-pass hepatic metabolism decreases oral bioavailability to 40 to 75%. Serum concentrations peak in 0.5 to 4 hours after an oral dose. The apparent volume of distribution of 11 to 25 L/kg is consistent with the high degree of lipophilicity of the drug and indicates extensive extravascular localization at steady state. Haloperidol circulates in blood predominantly (90 to 94%) bound to plasma proteins. Renal excretion of the parent drug is negligible, and clearance occurs almost exclusively by hepatic metabolism. Unlike the phenothiazines that produce an array of active metabolites, only one active metabolite of haloperidol has been identified to date. This metabolite, reduced haloperidol, is produced by hydroxylation of haloperidol and retains only approximately 10% of the pharmacologie activity of the parent drug. In patients with normal liver function,