Effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for hemorrhoidal symptoms: a prospective, observational study.

BACKGROUND AND AIMS: A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice. METHODS: Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined. RESULTS: Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated. CONCLUSIONS: The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.

Sucralfate as an Adjunct to Analgesia to Improve Oral Intake in Children With Infectious Oral Ulcers: A Randomized, Double-Blind, Placebo-Controlled Trial.

STUDY HYPOTHESIS: We hypothesized that sucralfate along with oral analgesics (acetaminophen or ibuprofen) administered in the emergency department leads to a clinically significant improvement in oral intake in children with acute infectious oral ulcers. METHODS: This was a randomized, double-blind, placebo-controlled trial of sucralfate versus placebo conducted between 2017 and 2018 in an urban pediatric emergency department. Children aged 6 months to 5 years with acute, infectious oral ulcers and poor oral intake received either acetaminophen at 15 mg/kg or ibuprofen at 10 mg/kg and were then randomized to receive sucralfate at 20 mg/kg per dose up to 1 g or a placebo solution. The primary outcome was oral fluid intake within 60 minutes of medication administration. The secondary outcomes were repeat ED visits, length of stay in ED, intravenous hydration rate, admission rate, adverse event rate, and emergency physician's determination of the adequacy of oral intake. RESULTS: One hundred subjects with mild dehydration (clinical dehydration score of 1) and a median age of 1.38 years were enrolled and analyzed (49 in the sucralfate group and 51 in the placebo group). Oral intake 1 hour after drug administration was similar in both the groups: the median intake in the sucralfate group was 9.7 mL/kg and 10.7 mL/kg in the placebo group (difference -1 mL/kg; 95% confidence interval [CI] -2.0 to 4.8). According to the emergency physician's report, the secondary outcomes were significant only for adequate oral intake: 71% in the sucralfate group versus 88% in the placebo group (difference -16.8%; 95% CI -32.2 to -1.4). CONCLUSION: Sucralfate as an adjunct to oral analgesics was not superior to placebo in improving oral intake in children with acute oral infectious ulcers.

Evaluation of the efficacy of topical sucralfate on healing haemorrhoidectomy incision wounds and reducing pain severity: A randomised clinical trial.

The healing of haemorrhoidectomy wounds is a main concern of surgeons and patients. Various modalities can improve the quality of wound care after surgery. Antibiotics and topical agents, such as solutions and ointments, have been evaluated. The current research investigates the effects of sucralfate ointment on wound healing (epithelialisation) and postoperative pain after open haemorrhoidectomy. This trial involves two groups of randomly collected patients (n = 40) who underwent open haemorrhoidectomy surgery by the Milligan-Morgan method. A 10% topical sucralfate ointment was applied to the investigated group's wounds, while the control group patients used Vaseline as a placebo. The present work measured the two outcomes as follows: pain severity by a Visual Analogues Scale (VAS) score and epithelialisation by a surgeon's visual inspection. During the postoperative phase, the mean VAS was 3.70 for the investigated group and 6.90 for the control group. On the average, the completion of epithelialisation for the investigated group was on day 13 as opposed to day 20 for the control group. The topical application of sucralfate ointment on post-haemorrhoidectomy wound is an effective method for the promotion of healing, also lessens the severity of pain, and reduces the need for analgesics.

L-arginine-induced esophagitis, report of six cases.

Background: Drug-induced esophagitis is an uncommon diagnosis in the pediatric population. The following is a report of six adolescents with L-arginine-induced esophagitis. Case reports: All patients were under treatment with L-arginine for short stature. After using the prescribed medication for 1-3 months, all cases started with severe retrosternal pain, odynophagia, and dysphagia. The upper gastrointestinal endoscopies showed ulcers located in the mid esophageal mucosa. Conclusions: In the presence of acute severe odynophagia, dysphagia, and retrosternal pain, drug-induced esophagitis should be considered as a possible diagnosis. Treatment includes liquid diet, pain control, sucralfate, omeprazole, and interruption of L-arginine. In addition, the physician should explain preventive measures focused on patient and family education on the drug side effects and precise instructions on how to take medications, as well as a careful balance of risk and benefits of any medication. At present, there are no clinical trials that support the use of L-arginine in treatment of short stature.

Introducción: La esofagitis inducida por medicamentos es un diagnóstico poco frecuente en pacientes pediátricos. A continuación, se describe una serie de seis casos de pacientes menores de 15 años con esofagitis inducida por L-arginina. Casos clínicos: Los seis casos se encontraban en tratamiento con L-arginina por talla baja e iniciaron con dolor retroesternal, odinofagia y disfagia de rápida instalación. Cuatro de ellos acudieron al servicio de urgencias por la intensidad de los síntomas. Los hallazgos en la endoscopia del tubo digestivo alto fueron úlceras en la mucosa del esófago a la altura del tercio medio, zona de estrechez natural por la compresión del bronquio izquierdo. Conclusiones: En presencia de odinofagia, disfagia, dolor retroesternal y el antecedente de la ingesta de L-arginina, la esofagitis inducida por fármacos debe considerarse como una posibilidad diagnóstica. El tratamiento está basado en el manejo del dolor, sucralfato, omeprazol, así como la suspensión del medicamento y medidas preventivas centradas en la educación del paciente y los familiares sobre los riesgos y beneficios de un medicamento y la forma correcta de administrarlo.

L-arginine-induced esophagitis, report of six cases / Reporte de seis casos de esofagitis inducida por L-arginina

Abstract Background: Drug-induced esophagitis is an uncommon diagnosis in the pediatric population. The following is a report of six adolescents with L-arginine-induced esophagitis. Case reports: All patients were under treatment with L-arginine for short stature. After using the prescribed medication for 1-3 months, all cases started with severe retrosternal pain, odynophagia, and dysphagia. The upper gastrointestinal endoscopies showed ulcers located in the mid esophageal mucosa. Conclusions: In the presence of acute severe odynophagia, dysphagia, and retrosternal pain, drug-induced esophagitis should be considered as a possible diagnosis. Treatment includes liquid diet, pain control, sucralfate, omeprazole, and interruption of L-arginine. In addition, the physician should explain preventive measures focused on patient and family education on the drug side effects and precise instructions on how to take medications, as well as a careful balance of risk and benefits of any medication. At present, there are no clinical trials that support the use of L-arginine in treatment of short stature.

Resumen Introducción: La esofagitis inducida por medicamentos es un diagnóstico poco frecuente en pacientes pediátricos. A continuación, se describe una serie de seis casos de pacientes menores de 15 años con esofagitis inducida por L-arginina. Casos clínicos: Los seis casos se encontraban en tratamiento con L-arginina por talla baja e iniciaron con dolor retroesternal, odinofagia y disfagia de rápida instalación. Cuatro de ellos acudieron al servicio de urgencias por la intensidad de los síntomas. Los hallazgos en la endoscopia del tubo digestivo alto fueron úlceras en la mucosa del esófago a la altura del tercio medio, zona de estrechez natural por la compresión del bronquio izquierdo. Conclusiones: En presencia de odinofagia, disfagia, dolor retroesternal y el antecedente de la ingesta de L-arginina, la esofagitis inducida por fármacos debe considerarse como una posibilidad diagnóstica. El tratamiento está basado en el manejo del dolor, sucralfato, omeprazol, así como la suspensión del medicamento y medidas preventivas centradas en la educación del paciente y los familiares sobre los riesgos y beneficios de un medicamento y la forma correcta de administrarlo.

Anesthetic Implications of the New Guidelines for Button Battery Ingestion in Children.

Button battery ingestions result in significant morbidity and mortality in children-before, during, and even after removal. The injuries created by a button battery lodged in the esophagus develop rapidly and can be severe. The current of the button battery, conducted through saliva and the tissue drives a highly alkaline caustic injury, leading to liquefactive tissue necrosis. In June 2018, new guidelines were released from the National Capital Poison Center, which include the use of preoperative protective, pH-neutralizing and viscous barrier interventions with honey and/or sucralfate administered within 12 h of ingestion. In addition, the use of postremoval irrigation of the esophagus with 50-150 mL 0.25% acetic acid is done in the operating room to help neutralize the site of tissue injury. Given that anesthesiologists play an important role in the management of esophageal foreign body removal, the entire specialty needs to be aware of the supporting data behind this and general perioperative considerations for management and potential complications of button battery ingestion.

Randomized controlled trial of topical mupirocin versus mupirocin with sucralfate combination in chronic skin ulcers.

OBJECTIVES: The objective of this study was to carry out a head-to-head comparison of topical sucralfate combined with mupirocin versus mupirocin alone in the treatment of chronic skin ulcers with respect to both effectiveness and safety. MATERIALS AND METHODS: A parallel-group, open-label, randomized, controlled trial (CTRI/2015/12/006443) was carried out with patients suffering from skin ulcers of Wagner grading 1 or 2 persisting for over 4 weeks. Ninety-six patients were recruited in total, and the modified intention-to-treat analysis dataset included 44 participants treated with mupirocin 2% and 46 treated with combined mupirocin 2% and sucralfate 7% ointment. Both medications were applied topically thrice daily for 6 weeks. Ulcer area assessed using millimeter graph paper and wound infection score assessed on a three-point scale were effectiveness measures. Treatment-emergent adverse reactions that were reported by patients or observed by the investigators were recorded. RESULTS: The median ulcer area was significantly reduced in the combined treatment group at the end of treatment. Clinically, 41.3% of the participants in the combined group showed complete ulcer healing at 6 weeks compared to 18.18% in the mupirocin alone group (P = 0.022). The wound infection score declined significantly from baseline by the end of 3 weeks of treatment in both the groups. The frequency of qualitative wound attributes, namely pain, discharge, and erythema, remained comparable between the groups except for discharge which disappeared completely from all remaining ulcers in the combined group but was still present in 11.36% of the participants treated with mupirocin alone (P = 0.025) at 6 weeks. Adverse events were few, all local, mild, and tolerable. CONCLUSIONS: The wound healing effect of topical sucralfate adds to the antimicrobial effect of mupirocin toward the overall improvement of chronic skin ulcers. The effect of combined topical treatment needs comparison with other topical medications and wound healing strategies.

Misoprostol is superior to combined omeprazole-sucralfate for the treatment of equine gastric glandular disease.

BACKGROUND: Previous studies have demonstrated a poor response to healing of gastric glandular lesions with oral omeprazole and other medications. OBJECTIVES: To evaluate the efficacy of two novel treatments (misoprostol [M] and combined omeprazole-sucralfate [OS]) in horses for gastric glandular disease. STUDY DESIGN: Prospective, clinical study. METHODS: Sixty-three sports horses with grade >1/4 glandular disease were identified by gastroscopy. Horses received either 5 µg/kg of misoprostol per os BID 1 h prior to feeding or a combination of 4 mg/kg enteric coated omeprazole per os SID and 12 mg/kg sucralfate per os BID where drugs were given 1 h prior to feeding and sucralfate given 60 min after omeprazole; allocation was dependent upon centre. Gastroscopy was repeated at 28-35 days. Evaluators of the gastroscopy images were blinded to the treatments the horses received and images were reviewed independently. RESULTS: The most common presenting sign in both treatment groups was poor performance (Overall - 65.1%; M - 60.5% and OS - 75%). Overall healing (P<0.001; OR = 11 [2.8-45]) and improvement (P = 0.006; OR = 11 [1.9-59]) of lesions were associated with resolution of clinical signs. Misoprostol was shown to be superior to combined omeprazole-sucralfate both for healing (M - 72% [95% CI 43-67] and OS - 20% [95% CI 7-41]; P<0.001) and improvement (M - 98% [95% CI 90-100] and OS - 65% [95% CI 43-83]; P<0.001). MAIN LIMITATIONS: Relatively small, clinical study, reliance on client questionnaire data, clients not blinded to the treatments the horse received, diet could have affected drug pharmacodynamics although mimics clinical practice and no validated scoring system available for glandular lesions. CONCLUSIONS: These results suggest that gastric glandular disease does indeed result in clinical signs. In this population of horses, misoprostol was superior to omeprazole and sucralfate and warrants further evaluation in a large scale, multi-centre trial.

ACVIM consensus statement: Support for rational administration of gastrointestinal protectants to dogs and cats.

The gastrointestinal (GI) mucosal barrier is continuously exposed to noxious toxins, reactive oxygen species, microbes, and drugs, leading to the development of inflammatory, erosive, and ultimately ulcerative lesions. This report offers a consensus opinion on the rational administration of GI protectants to dogs and cats, with an emphasis on proton pump inhibitors (PPIs), histamine type-2 receptor antagonists (H2 RAs), misoprostol, and sucralfate. These medications decrease gastric acidity or promote mucosal protective mechanisms, transforming the management of dyspepsia, peptic ulceration, and gastroesophageal reflux disease. In contrast to guidelines that have been established in people for the optimal treatment of gastroduodenal ulcers and gastroesophageal reflux disease, effective clinical dosages of antisecretory drugs have not been well established in the dog and cat to date. Similar to the situation in human medicine, practice of inappropriate prescription of acid suppressants is also commonplace in veterinary medicine. This report challenges the dogma and clinical practice of administering GI protectants for the routine management of gastritis, pancreatitis, hepatic disease, and renal disease in dogs and cats lacking additional risk factors for ulceration or concerns for GI bleeding. Judicious use of acid suppressants is warranted considering recent studies that have documented adverse effects of long-term supplementation of PPIs in people and animals.

Topical sucralfate cream treatment for aplasia cutis congenita with dystrophic epidermolysis bullosa: a case study.

Bart syndrome consists of aplasia cutis congenita (ACC) and dominant or recessive dystrophic epidermolysis bullosa (DEB), associated with skin fragility and nail dysplasia. ACC in DEB is thought to be caused by trauma, the most cited cause being in utero formation of bullae consequent to friction of the limbs. Epidermolysis bullosa (EB) refers to a hereditary mechanobullous disease following trauma, characterised by formation of blisters on the skin and mucous membranes. There are four categories of the disease, including epidermolysis bullosa simplex, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa and Kindler syndrome. Infection, sepsis and death may occur as a consequence of generalised blistering with complication. We present the case of a newborn diagnosed with DEB and whose lesions became almost fully epithelialised after treatment with 10% topical sucralfate.

Endoscopic Management of Recalcitrant Marginal Ulcers by Covering the Ulcer Bed.

BACKGROUND: Management options for marginal ulcers (MU) vary from medical therapy to revision surgery. Medical therapy is often ineffective and revision surgery is associated with a high morbidity and possible recurrence. AIMS: To evaluate technical feasibility, efficacy, and safety of endoscopic management of MU by covering the ulcer bed using oversewing and/or deploying a fully covered self-expandable metallic stent (FCSEMS). METHODS: Medical records of consecutive patients who underwent endoscopic suturing and/or FCSEMS deployment for recalcitrant MU between August 2016 and June 2017 at a single academic center were reviewed. Recalcitrant MU was defined as an ulcer that persists after 6 to 8 weeks despite maximal medical therapy (open capsule PPI, 40 mg bid as well as sucralfate qid), cessation of smoking and nonsteroidal anti-inflammatory drugs (NSAIDs), and Helicobacter pylori eradication. RESULTS: Eleven patients (age range 31-60; all females) with mean BMI of 27.72 ± 5.93 kg/m2 underwent endoscopic suturing and/or stent deployment for recalcitrant MU with abdominal pain at a median of 50 months (range 3-120) post-Roux-en-Y gastric bypass (RYGB). Seven patients were managed by oversewing, two were managed by FCSEMS, and two patients required both. Technical success was 100%. All patients reported resolution of abdominal pain at 1 week. Surveillance endoscopy performed in 10/11 (90.9%) patients at 8 weeks revealed complete ulcer healing in 9/10 (90%). No adverse events were reported. CONCLUSION: Endoscopic management is an effective and safe method to treat MU and should be considered an alternative to surgical revision. It appears effective for perforated and recalcitrant MU.

Effect of sucralfate on gastric permeability in an ex vivo model of stress-related mucosal disease in dogs.

BACKGROUND: Sucralfate is a gastroprotectant with no known systemic effects. The efficacy of sucralfate for prevention and treatment of stress-related mucosal diseases (SRMD) in dogs is unknown. HYPOTHESIS/OBJECTIVES: To develop a canine ex vivo model of SRMD and to determine the effect of sucralfate on mucosal barrier function in this model. ANIMALS: Gastric antral mucosa was collected immediately postmortem from 29 random-source apparently healthy dogs euthanized at a local animal control facility. METHODS: Randomized experimental trial. Sucralfate (100 mg/mL) was applied to ex vivo canine gastric mucosa concurrent with and after acid injury. Barrier function was assessed by measurement of transepithelial electrical resistance (TER) and radiolabeled mannitol flux. RESULTS: Application of acidified Ringers solution to the mucosal side of gastric antrum caused a reduction in gastric barrier function, and washout of acidified Ringers solution allowed recovery of barrier function (TER: 34.0 ± 2.8% of control at maximum injury, 71.3 ± 5.5% at recovery, P < .001). Sucralfate application at the time of injury or after injury significantly hastened recovery of barrier function (TER: 118.0 ± 15.2% of control at maximum injury, P < .001 and 111.0 ± 15.5% at recovery, P = .35). CONCLUSIONS AND CLINICAL IMPORTANCE: Sucralfate appeared effective at restoring defects in gastric barrier function induced by acid and accelerating repair of tissues subjected to acid in this model, suggesting that sucralfate could have utility for the treatment and prevention of SRMD in dogs.

Continuous radiotelemetric monitoring of intragastric pH in a dog with peptic ulceration.

CASE DESCRIPTION A 6-year-old castrated male Boxer was evaluated for a 5-week history of frequent vomiting, melena, and signs of abdominal pain following accidental ingestion of 5 to ten 15-mg meloxicam tablets (approx ingested dose, 3.1 to 6.2 mg/kg [1.4 to 2.8 mg/lb]). CLINICAL FINDINGS Clinical signs persisted despite 3 weeks of treatment with sucralfate (41.8 mg/kg [19 mg/lb], PO, q 8 h) and omeprazole (0.8 mg/kg [0.36 mg/lb], PO, q 24 h). Results of a CBC and serum biochemical analysis were unremarkable. Abdominal ultrasonography revealed peptic ulceration, and esophagogastroduodenoscopy confirmed the presence of severe proximal duodenal ulceration. TREATMENT AND OUTCOME A radiotelemetric pH-monitoring capsule was placed in the gastric fundus under endoscopic guidance for continuous at-home monitoring of intragastric pH and response to treatment. Treatment was continued with sucralfate (as previously prescribed) and omeprazole at an increased administration frequency (0.8 mg/kg, PO, q 12 h). Intragastric pH was consistently ≥ 3.0 for > 75% of the day during treatment, with the exception of 1 day when a single dose of omeprazole was inadvertently missed. Ulceration and clinical signs completely resolved. CLINICAL RELEVANCE Continuous radiotelemetric monitoring of intragastric pH in the dog of this report was useful for confirming that treatment achieved a predetermined target pH and for demonstrating the impact of missed doses. Duodenal ulceration resolved with twice-daily but not once-daily omeprazole administration. Findings suggested that twice-daily administration of omeprazole may be necessary to achieve this target pH and that a pH ≥ 3.0 for 75% of the day may promote healing of peptic ulcers in dogs.

Complementarity of in vitro and in vivo models for the evaluation of gastro-protective effects of pharmacological substances.

Gastric mucosa is frequently exposed to various gastric irritants, and there is a continuing requirement to develop new gastro-protective agents. This study compares the effects of three such agents, sucralfate, rebamipide, and cimetidine in both in vivo and in vitro indomethacin-induced gastric damage models. For the in vivo approach, rats were orally administered sucralfate, rebamipide, and cimetidine at 300 mg/kg before an acute dose of indomethacin (30 mg/kg). Gastric lesions were then macroscopically examined. For the in vitro approach, gastric mucosal cells were incubated with sucralfate (3 and 5 mg/mL), rebamipide (0.3 and 1 mm), and cimetidine (10 and 50 µg/mL) before exposure to indomethacin (3.8 mm). The release of lactate dehydrogenase (LDH) and mitochondrial function were then measured. Sucralfate, rebamipide, and cimetidine displayed gastro-protective effects in vivo (decreased number of gastric ulcers: -50% P < 0.05, -22% NS, and -69% P < 0.05, respectively, and reduced length of gastric lesions: -62% P < 0.05, -29% NS, and -70% P < 0.001, respectively). Cell damage induced by indomethacin in vitro was inhibited by sucralfate (LDH release) and by rebamipide and cimetidine (mitochondrial function and LDH release). In contrast, sucralfate accentuated the indomethacin-induced decrease in mitochondrial function. Although cultured gastric cells offer a promising tool for evaluating the cytotoxic or protective effects of test compounds, data from in vivo models are still needed to confirm in vitro data. Using both approaches provides more comprehensive insight into the effects of test compounds on the gastric mucosa.

Antiseptics and Antibiotics for Surgical Wounds Healing by Secondary Intention: Summary of a Cochrane Review.

Clinical Question: Do antiseptics and antibiotics benefit surgical wounds healing by secondary intention (SWHSI)? Bottom Line: No high-quality randomized clinical trials have addressed this question. Current evidence is limited and insufficient; it is uncertain whether treating SWHSI with antiseptics or antibiotics is beneficial.

Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.

Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.

Novel self-assembled mesalamine-sucralfate complexes: preparation, characterization, and formulation aspects.

Two well-known active agents, mesalamine (MES) and sucralfate (SUC), were investigated for possible utilization as fixed-dose combination product. The anti-inflammatory action of MES in association with bioadhesiveness and mucosal healing properties of SUC were considered promising for the development of a new compound containing both molecules, aimed as an improved treatment of ulcerative colitis. The present study investigates the capacity of the two active agents to interact and generate a new and stable entity via self-assembling. Spray-drying was used to co-process the two active principles from an aqueous mixture where the ratio MES:SUC was in the range 25:75, 50:50, and 75:25. The structural data (X-Ray, FTIR, SEM, DSC, and (1)H NMR) have shown that MES and SUC are interacting leading to complexes with properties differing from those of each separate active agent and from their physical blends. (1)H NMR results indicated that complexation occurred when the aqueous suspensions of drugs were mixed, prior to spray-drying. Drug-drug self-assembling was the driving mechanism in the formation of the new entity. Based on the structural data, a hypothetical structure of the complex was proposed. Co-processing of MES and SUC represents a simple and useful procedure to prepare new self-assembled compounds by valorizing the ionic interactions between the two entities. Preliminary studies with oral solid dosage forms based on MES-SUC complexes tested in vitro have shown a controlled MES release, opening the perspective of a new colon-targeted delivery system and a novel class of compounds with therapeutic application in inflammatory bowel diseases.

Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs.

BACKGROUND: Sucralfate impairs absorption of ciprofloxacin and other fluoroquinolones in humans, but no sucralfate-fluoroquinolone interaction has been reported in dogs. Veterinary formularies recommend avoiding concurrent administration of these medications, which might impact compliance, therapeutic success, and resistance selection from fluoroquinolones. OBJECTIVES: To determine whether a drug interaction exists when sucralfate is administered to fed dogs concurrently with ciprofloxacin or enrofloxacin, and whether a 2 hour delay between fluoroquinolone and sucralfate affects fluoroquinolone absorption. ANIMALS: Five healthy Greyhounds housed in a research colony. METHODS: This was a randomized crossover study. Treatments included oral ciprofloxacin (C) or oral enrofloxacin (E) alone, each fluoroquinolone concurrently with an oral suspension of sucralfate (CS, ES), and sucralfate suspension 2 hours after each fluoroquinolone (C2S, E2S). Fluoroquinolone concentrations were evaluated using liquid chromatography with mass spectrometry. RESULTS: Drug exposure of ciprofloxacin was highly variable (AUC 5.52-22.47 h µg/mL) compared to enrofloxacin (AUC 3.86-7.50 h µg/mL). The mean relative bioavailability for ciprofloxacin and concurrent sucralfate was 48% (range 8-143%) compared to ciprofloxacin alone. Relative bioavailability of ciprofloxacin improved to 87% (range 37-333%) when sucralfate was delayed by 2 hours. By contrast, relative bioavailability for enrofloxacin and concurrent sucralfate was 104% (94-115%). CONCLUSIONS AND CLINICAL IMPORTANCE: A possible clinically relevant drug interaction for the relative bioavailability of ciprofloxacin with sucralfate was found. No significant difference in bioavailability was documented for enrofloxacin with sucralfate. Further research is warranted in fasted dogs and clinical cases requiring enrofloxacin or other approved fluoroquinolones in combination with sucralfate.