Steady-State Pharmacokinetics of Haloperidol and Reduced Haloperidol in Schizophrenic Patients: Analysis of Factors Determining their Concentrations in Hair

Profiles of the steady‐state concentrations of haloperidol (HL) and its major metabolite, reduced haloperidol (RHL), in plasma versus time were determined in 10 Japanese patients whose schizophrenic symptoms were clinically controlled by fixed, oral maintenance doses (4–30 mg/day, three times a day) for >4 months. These data were used to determine the pharmacokinetic factor(s) that correlate best with HL and RHL concentrations in hair. The concentrations of HL and RHL in plasma or hair were simultaneously measured by high‐performance liquid chromatography with an electrochemical detector. The observed values of minimal and maximal concentrations in plasma (Cmin and Cmax' respectively) varied widely among patients: 3.0–22.9 and 6.2–32.7 ng/mL for HL and 2.8–21.4 and 5.7–33.3 ng/ml for RHL, respectively. The ratio of the area under the plasma concentration‐time curve (AUC) of RHL for 1 day to that of HL also ranged widely from 0.39 to 1.99 (1.04 ± 0.48, mean ± standard deviation). When the concentration of HL or RHL in hair was compared with the daily dose of HL and respective AUC, Cmax' or trough concentration in the plasma in the morning, the parameter that best correlated with the concentration of HL in hair was AUC. The concentration of RHL in hair correlated with all three parameters, but the correlation with AUC was better than that with Cmax. Therefore, the concentrations of these substances in hair were considered to be representative of their mean amounts in the body.