Pharmacokinetics of neuroleptics.

Older studies on neuroleptic pharmacokinetics had problems in methodology and laboratory techniques. High performance liquid chromatography (HPLC) and combinations of techniques are used now. Clozapine levels are related to dose, age, sex, and smoking. Fluphenazine decanoate gives more predictable levels than oral, and 25 mg/2 weeks is associated with the lowest relapse rate. A therapeutic window with haloperidol is not well established; increased side effects at higher doses may account for the worsening seen. Half-lives much longer than previously quoted are now described. Children and the elderly are more susceptible to side effects of neuroleptics. Studies of the neuroleptic threshold and brain imaging indicate that doses used today are excessive. Nonresponders can distort dose effect relationships. Plasma levels are not useful routinely; they are of use in ruling out pharmacokinetic factors in nonresponse and when side effects are severe.