Steady-state plasma level prediction for haloperidol from a single test dose

Due to large interindividual variabilities in kinetics of haloperidol (HPDL), empirically adjusting the dose to achieve steady-state plasma levels (Css) is a time consuming process. We report a method to individualize doses to achieve the desired Css from the observed plasma level 24 hours after a single test dose. Twenty-eight acutely psychotic patients, after up to 2 weeks of inhospital drug washout, received a 15-mg oral "test" dose of HPDL and 24- and 48-hour plasma levels were measured. They were then randomly assigned to empirically determined doses of HPDL (2, 4, or 10 mg b.i.d.) to achieve a low, medium, or high Css. The 24-hour plasma level after the test dose, the final Css, and the dose required to achieve that Css were analyzed by a linear regression model. The log Css in terms of the log dose revealed a strong linear relationship (R2 = .78, n = 28), which was further improved by the addition of the 24-hour log plasma level (R2 = .87).