The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA; Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland; Department of Psychiatry at the Donald and Barbara Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA.
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, PO Box 8905, Trondheim N-7491, Norway; Centre for Obesity Research, Clinic of Surgery, St. Olav University Hospital, PO Box 3250 Torgarden, Trondheim N-7006, Norway.
Epilepsy Res. 2024 Dec;208:107469. doi: 10.1016/j.eplepsyres.2024.107469. Epub 2024 Oct 20.
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.
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.
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.
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.
减重手术可能通过改变胃肠道生理来影响药物的药代动力学。迄今为止，针对减重治疗后一线抗癫痫药物（如拉莫三嗪和丙戊酸）的药代动力学变化，研究关注甚少。
在我们的前瞻性病例研究中，我们纳入了在挪威中部医院接受减重手术的拉莫三嗪或丙戊酸治疗的患者。在手术前和手术后 1、6 和 12 个月，使用间隔时间内的连续血样评估拉莫三嗪和丙戊酸的浓度。主要结局包括时间-浓度曲线下面积（AUC）的变化，次要结局包括全面的药代动力学分析。
纳入了 6 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 2 名接受丙戊酸治疗的患者（1 名接受 RYGB，1 名接受 SG）。术后经剂量调整的 AUC 值变化最大的是 RYGB 治疗的拉莫三嗪患者（术后 1 个月平均增加 38%，12 个月增加 32%）。接受丙戊酸治疗的患者中，AUC 值在术后 6 个月下降了 22%，12 个月下降了 30%。个体间差异很大。由于病例数较少，未进行正式的统计学检验。
拉莫三嗪和丙戊酸的术后药代动力学变化是适度的，但对于 RYGB 治疗的患者，拉莫三嗪的变化可能大于 SG 治疗的患者。鉴于个体间差异很大，在接受减重手术后，应使用治疗药物监测来捕获药代动力学变化并指导剂量调整。
