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.