Epidemiologic investigation of the relative clearance of haloperidol by mixed-effect modeling using routine clinical pharmacokinetic data in Japanese patients

The steady-state trough concentrations of haloperidol were studied to clarify the role of the characteristics of Japanese patients in estimating haloperidol dosing regimens by using routine therapeutic drug-monitoring data. Nonlinear mixed-effects modeling (NONMEM) was used to estimate the effect of a variety of developmental and demographic factors on haloperidol clearance values using 270 serum level measurements obtained from 191 patients during their clinical course. The final model describing haloperidol's relative clearance was CL = 0.74 · TBW^0.594 · DOSE^0.326 · 1.32(CO1) · 0.867(AGE), where CL is clearance (measured in liters per hour), TBW is the total body weight (in kilograms), DOSE is the daily dose of haloperidol (in grams per kilogram per day), CO1 = 1 for concomitant administration of antiepileptic drugs (phenobarbital, phenytoin, or carbamazepine) and CO1 = 0 otherwise, and AGE = 1 for patients aged 55 years or older and AGE = 0 otherwise. Concomitant administration of haloperidol and antiepileptic drugs resulted in a 32% increase in haloperidol clearance. Patients aged 55 years or older showed a 13.3% reduction in clearance values compared with the younger population.