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Prolonged Pharmacologic Activity of Neuroleptic Drugs

John W. Hubbard, PhD; Derek Ganes, MSc; Kamal K. Midha, DSc
Arch Gen Psychiatry. 1987;44(1):99-100. doi:10.1001/archpsyc.1987.01800130111024.
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To the Editor.—  Campbell and Baldessarini1 described an experiment in which they administered moderatesingle doses of haloperidol to rats and found that the behavioral response to the dopamine agonist apomorphine was reduced significantly for at least one month. They commented that the plasma elimination half-life values of neuroleptic drugs are usually reported in the range of 20 to 40 hours, whereas the apparent half-life for recovery of normal response to apomorphine was 12.8 days. Moreover, Sedval and colleagues2 also showed a lack of concordance between dopamine D2 receptor occupancy in the brains of schizophrenics and plasma haloperidol levels following the withdrawal of the drug.

Subjects and Methods.—  Recently, we measured levels of haloperidol and reduced haloperidol in the plasma of healthy volunteers after single oral doses of 5 mg of haloperidol. It is standard practice in single-dose pharmacokinetic studies to follow plasma levels for three to


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