Kinetics and clinical evaluation of haloperidol decanoate loading dose regimen

We have evaluated the efficacy and safety of different dosing regimens of haloperidol decanoate (HLD). Eighteen patients were evaluated as part of our ongoing Therapeutic Drug Monitoring Program. Diagnoses were chronic schizophrenia (n = 12), bipolar with psychosis (n = 3), and others (n = 3). Patients were assessed prior to each HLD dose using the Clinical Global Impressions (CGI) rating scale. The total monthly HLD dose for our population was calculated based on a target conversion ratio of 20 times the previously administered oral haloperidol dose given in divided doses of 100 mg to 150 mg every 3 to 7 days until the full amount was administered. This HLD dosing pattern was repeated during the second month, but at a lower dose to compensate for drug accumulation. Despite this loading dose paradigm, significantly greater haloperidol plasma concentrations were present during oral haloperidol than during the first month of HLD therapy. This regimen achieves therapeutically equivalent plasma concentrations (Cps) more rapidly following conversion from oral haloperidol than standard dosing procedures. A series of cases and pharmacokinetic simulations are used to illustrate the therapeutic relationship of dosing to plasma concentrations.