Daily dosing frequency as a determinant of clozapine concentration-to-dose ratio: Data from a therapeutic drug monitoring service (2019-2022).

BACKGROUND AND AIMS

Daily dosing frequency is an important factor influencing the plasma concentration of clozapine. This study investigated pharmacokinetic parameters in different daily dosing frequency regimens of clozapine in a naturalistic therapeutic drug monitoring sample to establish the necessary clozapine dosage to achieve plasma levels of 350-600 ng/mL in the Chinese population.

STUDY DESIGN

A single-center, retrospective, cross-sectional study was conducted at Xi'an Mental Health Center in China, where data on clozapine-treated patients between 2019 and 2022 were collected. The clozapine concentration-to-dose (C/D) ratios were compared between subgroups receiving different dosing regimens (once, twice, or three times per day) using Kruskal-Wallis H and Mann-Whitney U-tests.

STUDY RESULTS

The Kruskal-Wallis H test indicated significant variations in the C/D ratios among the three groups (p < 0.001). These findings were also consistent with the sex and age subgroup analyses. The receiver operating characteristic (ROC) analysis revealed that the twice-daily group required a daily clozapine dose of 125-225 mg to achieve the expected therapeutic reference concentration, with a corresponding clozapine C/D ratio of 1.6-2.8. The daily dose needed to reach therapeutic clozapine levels was higher in men than in women and in patients aged ≤ 44 years than in those aged ≥ 45 years.

CONCLUSIONS

The daily clozapine dosing frequency is an important factor influencing the pharmacokinetic profile of clozapine. Large-scale, multicenter, prospective studies are needed to validate the clinically significant results of this study by administering the same total daily dose at different daily dosing frequencies.