A Potential Role of Ethosuximide and Pentoxifylline in Relieving Abdominal Pain in Irritable Bowel Syndrome Patients Treated with Mebeverine: A Randomized, Double-Blind, Placebo-Controlled Trial
Sahar M El-Haggar,1 Sahar K Hegazy,1 Sherief M Abd-Elsalam,2 Eslam B Elkaeed,3 Ahmed A Al-Karmalawy,4 Mostafa M Bahaa5 1Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, El-Gharbia Government, Tanta, 31527, Egypt; 2Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Tanta University, Tanta, 315274, Egypt; 3Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, 13713, Saudi Arabia; 4Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt; 5Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, EgyptCorrespondence: Mostafa M Bahaa, Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt, Tel +201025538337, Email mostafabahaamnf@gmail.com; mbahaa@horus.edu.egBackground and Purpose: Irritable bowel syndrome (IBS) is defined as an association of chronic abdominal pain with bowel habit abnormalities, without clear organic dysfunction. T-type calcium channels and low-grade mucosal inflammation are linked to abdominal pain; however, medical treatments for IBS abdominal pain are largely ineffective. In this study, we investigated if pentoxifylline (PTX) and ethosuximide could potentially alleviate abdominal pain in patients with IBS treated with mebeverine.Methods: We recruited 150 patients from Tanta University Hospital to this randomized, prospective, and double blinded study. Patients were randomly allocated to three groups (n = 50). Group 1 (mebeverine) received 135 mg mebeverine three times/day (t.i.d). Group 2 (ethosuximide group) received 135 mg mebeverine t.i.d plus 250 mg ethosuximide twice daily (b.i.d) and group 3 (PTX group) received 135 mg mebeverine t.i.d plus 400 mg PTX b.i.d. Patients were assessed by a gastroenterologist at baseline and 6 months after therapy. Serum interleukin-8 (IL-8), IL-6, tumor necrosis-α (TNF-α), fecal myeloperoxidase, and fecal neutrophil gelatinase associated lipocalin (NGAL) levels were measured before and after therapy. The numeric pain rating scale (NRS) was also assessed before and after therapy.Primary Outcomes: Reduced NRS scores and abdominal pain relief.Secondary Outcomes: Decreased inflammatory biomarkers.Results: After 6 months, groups 2 and 3 showed a significantly greater reduction in serum IL-8, IL-6, TNF-α, fecal myeloperoxidase, and fecal NGAL levels when compared to group 1 after therapy. Both groups 2 and 3 showed significant reductions in NRS scores when compared to the group 1.Conclusion: Ethosuximide and PTX may be promising, novel adjunct drugs to antispasmodics for relieving abdominal pain in patients with IBS.Trial Registration: Identifier: NCT04217733.Graphical Abstract: Keywords: IBS, inflammation, pentoxifylline, Ca++ channels, ethosuximide
