Dose-dependent effect of lamotrigine on quetiapine serum concentration in patients using instant release tablets.

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2024-06-01 Epub Date: 2024-02-23 DOI:10.1007/s00228-024-03655-z

Kristine Hole, Silje K Lorentsen, Karoline L Nordby, Marie Slettvik, Ida Tg Sørum, Espen Molden, Tore Haslemo

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Abstract

Purpose: Lamotrigine was previously reported to reduce serum concentration of quetiapine. The aim of this study was to investigate whether lamotrigine dose or quetiapine formulation was of importance for the drug interaction.

Methods: Patients combining lamotrigine with quetiapine (cases) were included retrospectively from a routine therapeutic drug monitoring (TDM) service, as were a control group of patients using quetiapine without any interacting drugs. The case and control groups were divided into groups using immediate release (IR) and extended release (XR) quetiapine. The case group was further split into high-dose (> 200 mg/day) and low-dose (≤ 200 mg/day) lamotrigine users. Quetiapine concentration-to-dose (C/D) ratio and metabolite-to-parent ratio (MPR) were compared between the control group and dose-separated case groups using ANOVA test and t-tests.

Results: In total, 406 patients were included. The mean C/D ratio of IR quetiapine was 46% lower in the high-dose lamotrigine group compared with the control group (P < 0.001), while no interaction effect was present in the low dose lamotrigine group (P = 0.7). Regardless of lamotrigine dose, there was no difference in quetiapine C/D ratio for patients using the XR formulation (P = 0.4). The quetiapine MPR was unaffected regardless of formulation and lamotrigine dose (P ≥ 0.06).

Conclusion: The effect of lamotrigine in reducing quetiapine concentration is only significant for patients using quetiapine IR tablets who are treated with lamotrigine doses > 200 mg/day. Because of high variability in the interaction effect, TDM of quetiapine should be recommended during co-prescription of high-dose lamotrigine.

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拉莫三嗪对使用速释药片的患者体内喹硫平血清浓度的剂量依赖性影响。

目的：先前有报道称拉莫三嗪可降低喹硫平的血清浓度。本研究旨在探讨拉莫三嗪的剂量或奎硫平的配方对药物相互作用是否重要：方法：从常规治疗药物监测（TDM）服务中回顾性地纳入了拉莫三嗪与喹硫平合用的患者（病例），以及使用喹硫平而未服用任何相互作用药物的对照组患者。病例组和对照组分为使用速释（IR）和缓释（XR）喹硫平的两组。病例组又分为高剂量（> 200 毫克/天）和低剂量（≤ 200 毫克/天）拉莫三嗪使用者。采用方差分析和t检验比较了对照组和剂量分离病例组的喹硫平浓度剂量比（C/D）和代谢母体比（MPR）：结果：共纳入 406 名患者。与对照组相比，大剂量拉莫三嗪组 IR 喹硫平的平均 C/D 比值降低了 46%（P 结论：大剂量拉莫三嗪对 IR 喹硫平的疗效显著：拉莫三嗪降低喹硫平浓度的作用仅对使用拉莫三嗪剂量大于 200 毫克/天的喹硫平 IR 片剂的患者有显著影响。由于相互作用效果的变异性很大，因此在联合处方大剂量拉莫三嗪时，应建议对奎硫平进行TDM。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.