PLASMA REDUCED HALOPERIDOL HALOPERIDOL RATIOS IN SCHIZOPHRENIC-PATIENTS TREATED WITH HIGH DOSAGES OF HALOPERIDOL/

Plasma haloperidol (HL) and reduced haloperidol (RH) levels were measu red in 60 schizophrenic patients treated with high to very high HL dos es of 40-200 mg/day. Plasma samples were obtained at steady-state cond itions and 10-12 h after the evening dose and prior to the morning dos e. RH/HL ratios were shown to be dose-dependent. In the lowest dose gr oup of 40-45 mg/day, 77% of the patients had RH/HL ratios < 1.0. At th e higher dose of 60-80 mg/day, these results were reversed as 79% of t he 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 extrapyramida l side effects that were unresponsive to trihexyphenidyl. Therapeutic improvement was not observed in each patient. Based upon the dose-depe ndent increase in the RH/HL ratios in schizophrenic patients, the poss ible mechanism of a 'therapeutic' window for HL is discussed.