Abstract
Plasma haloperidol (HL) and reduced haloperidol (RH) levels were measured in 60 schizophrenic patients treated with high to very high HL doses of 40–200 mg/day. Plasma samples were obtained at steady-state conditions and 10–12 h after the evening dose and prior to the morning dose. RH/HL ratios were shown to be dose-dependent. In the lowest dose group of 40–45 mg/day, 77% of the patients had RH/HL ratios <1.0. At the higher dose of 60–80 mg/day, these results were reversed as 79% of the patients had RH/HL ratios >1.0. All patients with HL doses greater than 100 mg/day had RH/HL ratios >1.0. All patients safely tolerated the high haloperidol dosages and only five patients had extrapyramidal side effects that were unresponsive to trihexyphenidyl. Therapeutic improvement was not observed in each patient. Based upon the dose-dependent increase in the RH/HL ratios in schizophrenic patients, the possible mechanism of a ‘therapeutic’ window for HL is discussed.
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