Variability in Declining Haloperidol and Reduced Haloperidol Plasma Concentrations upon Haloperidol Cessation

Plasma concentrations of haloperidol and its reduced metabolite were measured in 6 schizophrenic patients after discontinuation of oral haloperidol treatment. Patients were on haloperidol 10mg twice daily for at least 2 to 4 weeks prior to cessation of treatment to ensure haloperidol steady-state concentrations had been achieved. Blood samples were obtained at 12, 24, 36, 60 and 84 hours following drug discontinuation. Haloperidol and reduced haloperidol were assayed by high-performance liquid chromatography with a lower limit of sensitivity of 0.2 μg/L and inter- and intra-assay coefficients of variation of less than 4 to 12% at 2 to 10 μg/L. Declining plasma concentrations of both haloperidol and reduced haloperidol were observed in each patient. Three of 5 patients had increased oscillations of either plasma haloperidol or reduced haloperidol concentrations at different times during the 84-hour period following withdrawal of haloperidol therapy. It is suggested that enterohepatic recycling could account for these oscillations.