Prediction of haloperidol steady-state levels in plasma after a single test dose

Because of large interindividual variabilities in the pharmocokinetics of haloperidol (HPDL), empirically adjusting the dose to achieve steady-state levels in plasma (C-ss) is a time-consuming process. We report a method to individualize dose to achieve a desired C-ss from an observed drug level 24 hours after a single 15-mg test dose of HPDL. Drug-free schizophrenic and schizo-affective patients were blindly and randomly assigned to achieve a low (< 5 ng/ml), medium (10-18 ng/ml), or high (> 25 ng/ml) C-ss range of HPDL. On day 1 of the study, each patient received an oral ''test'' dose of HPDL (15 mg), and blood was drawn 24 hours later to determine drug levels in plasma (C-24h). The first 34 patients (group I) were then maintained empirically on 2, 5 to 8, or 10 to 15 mg twice daily of oral HPDL concentrate for 5 days to achieve a low, medium, or high C-ss range, respectively. For the next 58 patients (group II), the dose of HPDL to achieve the assigned C-ss range was computed by using C-24h in a prediction formula. Application of the C-24h correctly predicted the maintenance dose required to achieve the C-ss in 73.2% of the cases. Further, there was a highly significant correlation (R(2) = 0.877, p < 0.0001) between the predicted dose and the actual dose required to achieve the targeted C-ss range. On the basis of these results, we have formulated a nomogram to help predict the maintenance dose required to achieve low, medium, or high HPDL targeted ranges at various C-24h values.