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 stea dy-state levels in plasma (C-ss) is a time-consuming process. We repor t a method to individualize dose to achieve a desired C-ss from an obs erved drug level 24 hours after a single 15-mg test dose of HPDL. Drug -free schizophrenic and schizo-affective patients were blindly and ran domly 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 pati ent received an oral ''test'' dose of HPDL (15 mg), and blood was draw n 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 achi eve a low, medium, or high C-ss range, respectively. For the next 58 p atients (group II), the dose of HPDL to achieve the assigned C-ss rang e 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 significa nt correlation (R(2) = 0.877, p < 0.0001) between the predicted dose a nd 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 ta rgeted ranges at various C-24h values.