Effects of Age, Sex, and Comedication on the Plasma Concentrations of Olanzapine in Chinese Patients With Schizophrenia Based on Therapeutic Drug Monitoring Data.

BACKGROUND

Olanzapine (OLA) is an atypical second-generation antipsychotic that exhibits significant pharmacokinetic variability. We retrospectively investigated the effects of age, sex, and specific comedications on OLA pharmacokinetics in Chinese patients with schizophrenia.

METHODS

Data on sex, age, and OLA dosage and steady-state plasma concentrations of 386 patients with schizophrenia (who have received OLA or a comedication of OLA with a psychotherapeutic drug) were collected and analyzed. The combined effects of dosage, age, sex, and comedication on OLA plasma levels were assessed via multiple linear regression analyses.

RESULTS

A daily dose of OLA was positively correlated with the drug's plasma concentrations. Overall, the OLA plasma concentrations and concentration-to-dose ratio (C/D) of the studied patients varied by 53.6- and 64.1-fold, achieving median values of 42.7 ng/mL and 2.73 (ng/mL)/(mg/d), respectively. Furthermore, a 1.27-fold higher estimated C/D in patients 60 years or older than in those younger than 60 years was identified. Female patients demonstrated a 33.6% higher C/D than in male patients. When coadministered with mood stabilizers (valproate or lithium), the median OLA C/D was 24.1% to 26.1% lower than that of OLA monotherapy. Interestingly, the OLA plasma concentration and C/D were not significantly affected by a comedication with aripiprazole, haloperidol, amisulpride, risperidone, clozapine, ziprasidone, citalopram, or buspirone.

CONCLUSIONS

The administered drug's dose was identified as an important determinant of the achieved OLA plasma concentration, with a positive correlation. The patients' sex and valproate (or lithium) comedication can significantly affect the C/D of OLA. Therapeutic drug monitoring should be routinely applied in cases of OLA-receiving patients with schizophrenia.