Tiorfan (racecadotril) / Bioprojet - LARVOL DELTA

Pharmacological and electrophysiological characterization of the novel Kv7 channel inhibitor racecadotril in Parkinson's disease. (PubMed, Neuropharmacology) - "Moreover, intraperitoneal administration of racecadotril in 8-week-old male C57BL/6 mice inhibited MPTP-induced motor dysfunction in this PD model, an effect that was blocked by the Kv7 channel opener retigabine (RTG). Taken together, our findings indicate that racecadotril is a potent inhibitor of Kv7.1, Kv7.2, Kv7.4 and Kv7.5 channels, which effectively ameliorates symptoms of PD in rodents."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Clinical practice guidelines for acute infectious diarrhea in children in China (2024). (PubMed, World J Pediatr) - "The updated guidelines address disputed treatments for acute infectious diarrhea through evidence-based revisions. Standardized etiological evaluations guide management. Probiotics are moderately advised for viral watery diarrhea; racecadotril remains unsupported. Zinc supplementation is recommended for children >6 months in deficient regions. Antibiotics are restricted to cases with dysenteric-like symptoms, suspected cholera with severe dehydration, or comorbidities."

Clinical guideline • Journal • Cholera • Gastrointestinal Disorder • Pediatrics

Racecadotril Versus Loperamide for Acute Diarrhea of Infectious Origin in Adults: A Systematic Review and Meta-Analysis. (PubMed, Health Sci Rep) - "Additionally, the analysis of secondary outcomes revealed varying effects on abdominal pain, constipation, and abdominal enlargement, with moderate heterogeneity observed (I² = 56%). Compared with loperamide, racecadotril is a better therapeutic option for adult diarrhea caused by infection."

Journal • Retrospective data • Review • Constipation • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Pain

CRISPR/Cas9-engineering of Kell null erythrocytes to unveil host targeted irresistible antimalarial. (PubMed, Commun Biol) - "Interestingly, individuals in malaria-endemic regions exhibit low Kell expression and activity, indicating a plausible Plasmodium-induced evolutionary pressure. Both thiorphan and its prodrug racecadotril, demonstrated potent antimalarial activity in vivo, highlighting Kell's protease role in invasion and proposing thiorphan as a promising host-oriented antimalarial therapeutic."

Journal • Infectious Disease • Malaria

Pharmacological Strategies for High-Output Ileostomies in Children: A Narrative Review. (PubMed, Acta Paediatr) - "Pharmacological options for the treatment of HOI in children are limited and evidence for their use is lacking. Research in paediatric HOI patients is needed to validate the use of pharmacotherapy in this patient group."

Journal • Review • CNS Disorders • Pediatrics • Psychiatry

Racecadotril in the management of diarrhea: an underestimated therapeutic option? (PubMed, Therap Adv Gastroenterol) - "Racecadotril has been shown to increase the likelihood of home management of AID, to reduce hospitalizations and parenteral rehydration needs resulting in healthcare costs reduction. The current new formulations require only two-daily doses for adults and the pediatric syrup should simplify its use."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Pediatrics

EFFICACY OF RACECADOTRIL IN A NEN PATIENT SUFFERING FROM THERAPY-REFRACTORY VIPOMA AND CARCINOID-SYNDROM (UEGW 2024) - "Of note, hormonal excess syndromes can have a greater impact on patients` morbidity and mortality than the tumor mass itself.Case presentation: We present the case of a 49-year-old male patient suffering from an oligo-metastatic ileal NEN, concurrently demonstrating vasointestinal peptide (VIP) and serotonin excretion, complicated by pulmonary tuberculosis, using Racecadotril as ultimate ratio.After the first cycle of Lutetium-177-DOTATATE peptide-radio-receptor therapy, the patient developed a severe watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome, despite receiving high-dose somatostatin analogues, everolimus, and telotristat ethyl, without any surgical options. This case report underscores racecadotril as an individualized, off-label treatment strategy for patients with severe VIPoma and serotonin-driven WDHA syndrome, where conventional therapeutic avenues have been exhausted. Further studies are warranted to potentially expand and license the use of..."

Clinical • Carcinoid Syndrome • Endocrine Cancer • Gastrointestinal Disorder • Infectious Disease • Metabolic Disorders • Neuroendocrine Tumor • Oncology • Respiratory Diseases • Solid Tumor • Tuberculosis • PENK

New and Emerging Therapeutic Drugs for the Treatment of Pulmonary Arterial Hypertension: A Systematic Review. (PubMed, Cureus) - "Several FDA-approved therapeutic options are available, including prostacyclin analogs (epoprostenol, iloprost, and treprostinil), the non-prostanoid IP receptor agonist selexipag, selective endothelin receptor antagonists (ERA) (ambrisentan, bosentan, and macitentan), phosphodiesterase 5 inhibitors (sildenafil and tadalafil), and the soluble guanylate cyclase (sGC) stimulator riociguat...The review found that while udenafil, imatinib, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were evaluated, imatinib was notably associated with adverse side effects. Conversely, udenafil, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were found to be safe, well-tolerated, and effective in improving hemodynamic measures and 6-MWDs. This study aims to summarize the developing treatment options currently under clinical trials, highlighting the need for further trials before their application in clinical practice."

Journal • Review • Cardiovascular • Fibrosis • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Efficacy of Racecadotril in a Patient Affected by a Therapy-Refractory VIPoma and Carcinoid Syndrome. (PubMed, JCEM Case Rep) - "After the first cycle of Lutetium-177-DOTATATE peptide-radio-receptor therapy, the patient developed a severe watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome, despite receiving high-dose somatostatin analogues, everolimus, and telotristat ethyl, without any surgical options. After 5 days of treatment, the WDHA syndrome exhibited sufficient control, facilitating the patient's discharge from the ICU. This case report underscores racecadotril as an individualized, off-label treatment strategy for patients with severe VIPoma and serotonin-driven WDHA syndrome, where conventional therapeutic avenues have been exhausted."

Journal • Carcinoid Syndrome • Critical care • Endocrine Cancer • Gastrointestinal Disorder • Infectious Disease • Metabolic Disorders • Neuroendocrine Tumor • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Tuberculosis • PENK

ERADICATE: Racecadotril Versus Standard Treatment in Decreasing the Duration of Acute Diarrhoea in Children (clinicaltrials.gov) - P1/2 | N=260 | Not yet recruiting | Sponsor: Liaquat National Hospital & Medical College

New P1/2 trial

Quantitation of thiorphan in human plasma using LC-MS/MS and its application to a bioequivalence study. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "This method proved stable under several conditions. The developed method worked well in a three-period pharmacokinetic bioequivalence study after a single oral administration of 100 mg racecadotril to 15 healthy Jordanian volunteers under fasting conditions."

Journal

DIVERSITY OF ASSESSMENT AND PRACTICE ON ACUTE GASTROENTERITIS: A NATIONAL SURVEY OF THAI PAEDIATRICIANS (ESPGHAN 2024) - "In the PG group, adjuvant medications such as racecadotril and diosmectite were administered more frequently (aOR 7.86, P = 0.009 and aOR 15.42, P < 0.001, respectively). Domperidone (52.4%) was the most common treatment for patients experiencing their first episode of vomiting... The national pediatricians' practices for acute gastroenteritis were examined in this survey. The majority of agreement was found in the areas of patient assessment, breastfeeding, fluid therapy's initial phase, and empirical antibiotic choices. The indications for investigation and the use of antiemetics, however, varied and might not have followed the Thai practice guideline."

Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hepatology • Hypotension • Pediatrics

Bioequivalence Study of Generic Racecadotril 100 mg Capsules Under Fasting Conditions (clinicaltrials.gov) - P1 | N=44 | Not yet recruiting | Sponsor: Pharma Nueva

New P1 trial

Evaluation of the clinical efficacy of racecadotril in the treatment of neonatal calves with infectious diarrhea. (PubMed, Pol J Vet Sci) - "We found that racecadotril was effective in improving both clinical recovery and feces consistency in neonatal calves with diarrhea caused by E. coli. As a result, it can be stated that racecadotril, which has an antisecretory effect, is beneficial in the treatment of bacterial diarrhea caused by such as E. coli."

Journal • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Rotavirus Infections • PENK

Influence of NEP Inhibition on Vascular Leak and Inflammation (NEPi-INFLAMMATION) (clinicaltrials.gov) - P=N/A | N=48 | Recruiting | Sponsor: Queen Mary University of London | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Inflammation • Pulmonary Disease • Respiratory Diseases

Racecadotril versus Loperamide in acute radiation enteritis: a randomized, double-blind, phase 3, non-inferiority trial. (PubMed, Int J Radiat Oncol Biol Phys) - "Rebound constipation was more in the Loperamide arm compared to Racecadotril (17.3 % vs 6.2%, p = 0.028) The non-inferiority of Racecadotril to Loperamide in acute radiation enteritis could not be demonstrated. However, Racecadotril can be the preferred drug of choice in acute radiation enteritis since Racecadotril does not affect bowel motility, achieved a high clinical success rate, similar to that of Loperamide, and was associated with lesser side effects."

Clinical • Head-to-Head • Journal • P3 data • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology

Influence of NEP Inhibition on Vascular Leak and Inflammation (NEPi-INFLAMMATION) (clinicaltrials.gov) - P=N/A | N=48 | Recruiting | Sponsor: Queen Mary University of London | Initiation date: May 2023 ➔ Aug 2023

Trial initiation date • Acute Respiratory Distress Syndrome • Inflammation • Pulmonary Disease • Respiratory Diseases • CCL2 • CXCL1 • CXCL8 • IL10 • IL6

Influence of NEP Inhibition on Vascular Leak and Inflammation (NEPi-INFLAMMATION) (clinicaltrials.gov) - P=N/A | N=48 | Recruiting | Sponsor: Queen Mary University of London | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2024 ➔ Jun 2025 | Initiation date: Jan 2023 ➔ May 2023 | Trial primary completion date: Jan 2024 ➔ Jan 2025

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Acute Respiratory Distress Syndrome • Inflammation • Pulmonary Disease • Respiratory Diseases • CCL2 • CXCL1 • CXCL8 • IL10 • IL6

Integrating metabolomics, bionics, and culturomics to study probiotics-driven drug metabolism. (PubMed, Front Pharmacol) - "However, a personalized effect was observed in the racecadotril-metabolizing activity of L. casei Zhang, depending on the individual's host gut microbiome composition. Based on data generated by our workflow, we proposed a possible mechanism of interactions among L. casei Zhang, racecadotril, and host gut microbiome, providing practical guidance for probiotic-drug co-treatment and novel insights into precision probiotics."

Journal

A single dose of ciprofloxacin reduces the duration of diarrhea among service members deployed in Africa. (PubMed, Infect Dis Now) - "A single dose of ciprofloxacin was effective and safe in treating uncomplicated diarrhea among service members in Africa."

Journal • Gastrointestinal Disorder • Infectious Disease

Influence of NEP Inhibition on Vascular Leak and Inflammation (NEPi-INFLAMMATION) (clinicaltrials.gov) - P=N/A | N=48 | Not yet recruiting | Sponsor: Queen Mary University of London

New trial • Acute Respiratory Distress Syndrome • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CCL2 • CXCL1 • CXCL8 • IL10 • IL6

National Consensus for the Management of Acute Gastroenteritis in Jordanian Children: Consensus Recommendations Endorsed by the Jordanian Paediatric Society. (PubMed, Int J Pediatr) - "Ondansetron, diosmectite, racecadotril, probiotics, and zinc can be considered adjunct to ORS, if needed. Local data gaps should be addressed. The clinical algorithm for the management of paediatric AGE could promote adherence to practice recommendations and by extension improve health outcomes in children."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Pediatrics • Rotavirus Infections

Evaluation of the Effect of Ethyl Acrylate-Methyl Methacrylate Copolymer in Racecadotril Dispersible Tablet. (PubMed, Turk J Pharm Sci) - "Our results demonstrated that a chemically long-term stable racecadotril dispersible tablet product, whose taste is efficiently masked using wet granulation method with an acceptable release profile was obtained with Eudragit NE 30D ratio higher than 1% and equal or lower than 10% by weight of racecadotril. The developed formulation can increase patient compliance."

Journal

A Multinational Chart Review to Examine Gastrointestinal Symptoms and Their Management in Patients Treated with Apremilast for Plaque Psoriasis (AAD 2022) - "The following GI symptoms were reported: ‒ Diarrhea (US: 67% [331/494]; France: 76% [97/128]) with median time from onset to resolution/improvement of 26 days (US) and 21 days (France) ‒ Nausea (US: 52% [255/494]; France: 34% [44/128]) with median time from onset to resolution/improvement of 21 days (US) and 24 days (France)Management strategies for diarrhea included pharmacologic (loperamide/bismuth subsalicylate/racecadotril) with or without non-pharmacologic (dietary modifications, taking with food)/fiber (US: 30% [99/331], France: 41% [40/97]) and non-pharmacologic only (US: 32% [105/331], France: 27% [26/97]). Recommendations to manage diarrhea and nausea after apremilast initiation with pharmacologic or non-pharmacologic strategies were effective and symptoms usually resolved within 3-4 weeks of onset."

Clinical • Review • Dermatology • Gastrointestinal Disorder • Immunology • Psoriasis

Can diarrhea affect the pharmacokinetics of racecadotril in neonatal calves? (PubMed, J Vet Pharmacol Ther) - "As in calves with infectious diarrhea, thiorphan in plasma was only detected in healthy calves from 0.25 to 1.5 h. Racecadotril showed a large distribution volume, rapid elimination, and low metabolism to thiorphan in healthy calves."

Journal • PK/PD data • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease • Rotavirus Infections