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

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2024-11-27 DOI:10.1016/j.cca.2024.120064

Jing Ding, Suo zhang, Luyao Li, Huan Xing, Yang Zhang, Zhuocheng Meng, Xiaohua Cui

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引用次数: 0

Abstract

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.

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.