Predicting pharmacokinetic stability by multiple oral administration of atypical antipsychotics.

Lower fluctuation, i.e., lower peak-to-trough plasma-concentration variation at steady-state pharmacokinetics, has several advantages for the treatment of schizophrenia with antipsychotics. The reduction of peak concentration can decrease the risk of dose-dependent side effects, such as extrapyramidal symptom and somnolence, and by contrast the increase in trough concentration can decrease the incidence of lack of efficacy due to subtherapeutic drug concentration. Using a one-compartment simulation technique with pharmacokinetic parameters of each atypical antipsychotic collected from package inserts, the fluctuation index was calculated. Among the antipsychotics, the indices varied from 0.018 to 1.9, depending on dosing regimens, formulations and several pharmacokinetic properties. The order of simulated fluctuation index is active-moiety aripiprazole (b.i.d.) <paliperidone extended release (q.d.) moiety aripiprazole (q.d.) moiety blonanserin (b.i.d.) <olanzapine (q.d.) moiety risperidone (b.i.d.) <amisulpride (q.d.) moiety risperidone (q.d.) <quetiapine (t.i.d.) <perospirone (t.i.d.) <quetiapine (b.i.d.). Since the fluctuation indices of aripiprazole and paliperidone extended-release are less than 0.2, which predominantly attributed to their long elimination half-lives, aripiprazole and paliperidone extended-release may have advantages in that the plasma concentration could be kept within appropriate therapeutic range.