Lamotrigine therapy in patients after bariatric surgery: Potentially hampered solubility and dissolution.

Bariatric surgery is an effective treatment of obesity and related comorbidities. With surgery, the stomach undergoes major anatomical/physiological changes that may affect the oral exposure of drugs, especially marginally soluble weak bases, such as lamotrigine. The aim of this work was to study the solubility/dissolution of lamotrigine in conditions simulating the stomach before vs. after bariatric surgery. Lamotrigine solubility was studied in-vitro, as well as ex-vivo in gastric content aspirated from patients before vs. after bariatric surgery. We then compared the dissolution kinetics of various marketed lamotrigine products in pre- vs. post-operative stomach conditions, different in volume, pH, agitation strength and speed. Decreased lamotrigine solubility with increasing pH (from 1.37 ± 0.09 (pH = 1) to 0.22 ± 0.03 mg/mL (pH = 7)) was obtained. Twelve-fold higher lamotrigine solubility was revealed in gastric content aspirated before vs. after surgery (8.5 ± 0.7 and 0.7 ± 0.01 mg/mL, respectively). Dissolution studies showed that only the lowest dose (25 mg) fully dissolved in the post-surgery stomach conditions, while at higher doses, lamotrigine tablet dissolution was impaired. Neither fast-dissolving tablet, nor tablet crushing, helped resolving this problem. Based on these results, and given that dissolution of the drug dose governs the subsequent absorption, close monitoring of this essential drug is advised after bariatric surgery.

Lithium Toxicity with Severe Bradycardia Post Sleeve Gastrectomy: a Case Report and Review of the Literature.

Lithium is one of the major treatment options in bipolar disorder. Bariatric surgery can significantly modify the oral bioavailability of drugs, and lithium is no exception; although in most cases drug absorption seems to decrease, in the case of lithium, toxicity is the risk. In this article, we describe a 61-year-old male patient presented with lithium toxicity, including newly diagnosed severe bradycardia requiring a permanent pacemaker, after undergoing sleeve gastrectomy. We discuss the mechanisms behind this case, provide potential solutions for clinicians treating bariatric patients with lithium, and review previous reports of lithium toxicity post bariatric surgery. Awareness of changes in drug absorption, particularly lithium, following bariatric surgery, is prudent and essential for optimal patient care. Close clinical and drug levels monitoring is strongly advised.