Pharmacokinetic interaction of quetiapine and lamotrigine - victim and perpetrator?

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY Expert Review of Clinical Pharmacology Pub Date : 2024-10-03 DOI:10.1080/17512433.2024.2410400

Florian Gilleßen, Arnim Johannes Gaebler, Ekkehard Haen, Georgios Schoretsanitis, Justyna Wozniak, Julia C Stingl, Michael Paulzen

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Abstract

Objective: We aimed to investigate the ambiguous findings of earlier research regarding the reduction of quetiapine plasma levels when combined with lamotrigine, most likely via UDP-glucuronosyltransferase induction by lamotrigine.

Methods: One thousand one hundred and fifty samples, divided into four groups of patients receiving either quetiapine immediate- (IR) or extended-release (XR) without or in combination with lamotrigine were compared regarding absolute and dose-adjusted plasma concentrations. Furthermore, samples of intra-individual controls were analyzed.

Results: Patients receiving quetiapine IR in combination with lamotrigine showed 31% lower plasma (p = 0.002) and 23% lower dose-adjusted plasma concentrations (p = 0.004) compared to those receiving IR monotherapy. The proportion of patients with quetiapine plasma concentrations below the lower limit of the therapeutic reference range was 50% and 30% in the combination group and in patients receiving monotherapy, respectively (p = 0.03). However, no significant differences regarding plasma concentration (p = 0.13) and dose-adjusted plasma concentration (p = 0.42) were observed in patients with combination vs. monotherapy with the XR formulation of quetiapine. In the intra-individual controls, no trends could be identified, possibly due to insufficient number of samples (p > 0.05).

Conclusions: The combination of quetiapine IR with lamotrigine is associated with significantly lower drug concentrations of quetiapine, potentially impacting quetiapine effectiveness. For quetiapine ER, a significant interaction is less likely.

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喹硫平与拉莫三嗪的药代动力学相互作用--受害者还是肇事者？

研究目的我们旨在研究早期研究中关于喹硫平与拉莫三嗪合用时血浆中喹硫平水平降低的模糊结论，这很可能是通过拉莫三嗪诱导UDP-葡萄糖醛酸转移酶所致：将接受喹硫平即释（IR）或缓释（XR）治疗但不与拉莫三嗪合用或与拉莫三嗪合用的患者分成四组，对一千一百五十份样本的绝对血浆浓度和剂量调整血浆浓度进行了比较。此外，还分析了个体内对照样本：结果：与接受IR单药治疗的患者相比，接受喹硫平IR联合拉莫三嗪治疗的患者血浆浓度低31%（p = 0.002），剂量调整后血浆浓度低23%（p = 0.004）。联合用药组和单药治疗组中，喹硫平血浆浓度低于治疗参考范围下限的患者比例分别为50%和30%（p = 0.03）。然而，在接受喹硫平XR制剂联合治疗与单药治疗的患者中，未观察到血浆浓度（p = 0.13）和剂量调整血浆浓度（p = 0.42）方面的明显差异。在个体内部对照中，可能由于样本数量不足（p > 0.05），未发现任何趋势：结论：喹硫平IR与拉莫三嗪合用时，喹硫平的药物浓度明显降低，可能会影响喹硫平的疗效。对于喹硫平 ER 而言，发生显著相互作用的可能性较小。

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

Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

7.30

自引率

2.30%

发文量

127

期刊介绍： Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.