袖带胃切除术和 Roux-en-Y 胃旁路术对拉莫三嗪和丙戊酸钠药代动力学的影响：一项队列研究。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research Pub Date : 2024-10-20 DOI:10.1016/j.eplepsyres.2024.107469

Georgios Schoretsanitis , Magnus Strømmen , Hege-Merete Krabseth , Olav Spigset , Arne Helland

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引用次数: 0

摘要

背景：减肥手术可能会通过改变胃肠道生理机能来影响药物的药代动力学。迄今为止，减肥治疗后拉莫三嗪和丙戊酸钠等一线抗癫痫药物的药代动力学变化很少受到研究关注：在前瞻性病例研究中，我们纳入了在挪威中部医院接受减肥手术的拉莫三嗪或丙戊酸钠治疗患者。在手术前、手术后1个月、6个月和12个月期间，通过连续血样评估拉莫三嗪和丙戊酸钠的浓度。主要结果包括时间-浓度曲线下面积（AUC）的变化，次要结果包括完整的药代动力学分析：结果：纳入了六名接受 Roux-en-Y 胃旁路术（RYGB）（n = 3）和袖状胃切除术（SG）（n = 3）的拉莫三嗪治疗肥胖患者，以及两名丙戊酸钠治疗患者（一名接受 RYGB，一名接受 SG）。接受拉莫三嗪治疗的 RYGB 患者术后剂量调整后的 AUC 值变化最大（术后 1 个月和 12 个月的平均增幅分别为 38% 和 32%）。在服用丙戊酸钠的患者中，6 个月后 AUC 值下降了 22%，12 个月后下降了 30%。个体间差异很大。由于病例较少，因此没有进行正式的统计学测试：拉莫三嗪和丙戊酸钠的术后药代动力学变化不大，但拉莫三嗪在接受 RYGB 治疗的患者中的变化可能大于接受 SG 治疗的患者。考虑到个体间的巨大差异，减肥手术后应使用治疗药物监测来捕捉药代动力学变化并指导剂量调整。

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Effects of sleeve gastrectomy and Roux-en-Y gastric bypass on pharmacokinetics of lamotrigine and valproate: A cohort study

Background

Bariatric surgeries may affect the pharmacokinetics of medications through alterations of the gastrointestinal physiology. Pharmacokinetic changes of first-line antiseizure medications such as lamotrigine and valproate following bariatric treatment have received little research attention so far.

Methods

In our prospective case study we included lamotrigine- or valproate-treated patients undergoing bariatric surgery at hospitals in Central Norway. Lamotrigine and valproate concentrations were assessed using serial blood samples over a dose interval, before and one, six and twelve months following surgery. Primary outcomes included changes in area under the time-concentration curve (AUC) with secondary outcomes comprising full pharmacokinetic profiling.

Results

Six lamotrigine-treated obese patients undergoing Roux-en-Y gastric bypass (RYGB) (n = 3) and sleeve gastrectomy (SG) (n = 3), as well as two valproate-treated patients (one undergoing RYGB and one SG) were included. Largest changes for dose-adjusted AUC values after surgery were seen in RYGB-treated patients on lamotrigine (average increases of 38 % one month and 32 % 12 months postoperatively). In the patients on valproate, AUC values were decreased by 22 % after 6 months and by 30 % after 12 months. The interindividual variation was high. Formal statistical testing was not done due to few cases.

Conclusion

Postoperative pharmacokinetic changes for lamotrigine and valproate were modest, but for lamotrigine changes may be larger in patients undergoing RYGB than in those undergoing SG. Given the substantial interindividual variation, therapeutic drug monitoring should be used to capture pharmacokinetic changes and guide dose adjustments after bariatric surgery.

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来源期刊

Epilepsy Research 医学-临床神经学

CiteScore

0.10

自引率

4.50%

发文量

143

审稿时长

62 days

期刊介绍： Epilepsy Research provides for publication of high quality articles in both basic and clinical epilepsy research, with a special emphasis on translational research that ultimately relates to epilepsy as a human condition. The journal is intended to provide a forum for reporting the best and most rigorous epilepsy research from all disciplines ranging from biophysics and molecular biology to epidemiological and psychosocial research. As such the journal will publish original papers relevant to epilepsy from any scientific discipline and also studies of a multidisciplinary nature. Clinical and experimental research papers adopting fresh conceptual approaches to the study of epilepsy and its treatment are encouraged. The overriding criteria for publication are novelty, significant clinical or experimental relevance, and interest to a multidisciplinary audience in the broad arena of epilepsy. Review articles focused on any topic of epilepsy research will also be considered, but only if they present an exceptionally clear synthesis of current knowledge and future directions of a research area, based on a critical assessment of the available data or on hypotheses that are likely to stimulate more critical thinking and further advances in an area of epilepsy research.