Cholestyramine Resin Research Articles

Development of a Rapid Analytical Method on UV Spectrophotometer for Analysis of Trace Level APIs Telmisartan in Cleaning Validation Sample

Since the 1990’s, cleaning validations have gained a lot of interest within pharmaceutical and bio-pharmaceutical companies. In 1988, the FDA experienced its first major incident with cross contamination traceable to inadequate cleaning and cleaning validation. The finished drug product, Cholestyramine Resin USP, was recalled due to contamination with low levels of intermediates and degradants from the production of agricultural pesticides. The cross-contamination was believed to have come from the use of drums in the production of the active pharmaceutical ingredient (API). These drums had previously been used to store solvents for the manufacture of agricultural pesticides at another plant. Extra pure methanol procured from Chempura Enterprises Indore of make Merck and Analytical Grade water procured from the SK Traders Indore M.P. Reference materials, Telmisartan from Axiom Analytical Services Indore M.P. HPLC grade methanol (MeOH), HPLC Grade Water were purchased from Chempura Enterprises Indore M.P.. All chemicals were used as received, without any further purification. In recent years, increased emphasis has been placed in pharmaceutical companies for implementing robust validated cleaning procedures. The cleaning procedure is one of the most important tasks to avoid contamination and cross- contamination of APIs in pharmaceutical products manufactured on the same equipment trains. The cleaning procedures must be supported byappropriate analytical methods and related sampling methodologies.

Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

Pien Tze Huang (PZH), a class-1 nationally protected traditional Chinese medicine (TCM), has been used to treat liver diseases such as hepatitis; however, the effect of PZH on the progression of sepsis is unknown. Here, we reported that PZH attenuated lipopolysaccharide (LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalling. Mechanistically, PZH stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation to induce the expression of A20, which could inhibit the activation of NF-κB and MAPK signalling. Knockdown of the bile acid (BA) receptor G protein-coupled bile acid receptor 1 (TGR5) in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction, as well as the LPS-induced inflammatory response, suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5. Consistently, deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20, the activation of NF-κB and MAPK signalling, and the production of proinflammatory cytokines, whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines. Overall, our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Divergence in aerobic capacity influences hepatic and systemic metabolic adaptations to bile acid sequestrant and short-term high-fat/sucrose feeding in rats.

High versus low aerobic capacity significantly impacts the risk for metabolic diseases. Rats selectively bred for high or low intrinsic aerobic capacity differently modify hepatic bile acid metabolism in response to high-fat diets (HFDs). Here we tested if a bile acid sequestrant would alter hepatic and whole body metabolism differently in rats with high and low aerobic capacity fed a 1-wk HFD. Male rats (8 mo of age) that were artificially selected to be high (HCR) and low-capacity runners (LCR) with divergent intrinsic aerobic capacities were transitioned from a low-fat diet (LFD, 10% fat) to an HFD (45% fat) with or without a bile acid sequestrant (BA-Seq, 2% cholestyramine resin) for 7 days while maintained in an indirect calorimetry system. HFD + BA-Seq increased fecal excretion of lipids and bile acids and prevented weight and fat mass gain in both strains. Interestingly, HCR rats had increased adaptability to enhance fecal bile acid and lipid loss, resulting in more significant energy loss than their LCR counterpart. In addition, BA-Seq induced a greater expression of hepatic CYP7A1 gene expression, the rate-limiting enzyme of bile acid synthesis in HCR rats both on HFD and HFD + BA-Seq diets. HCR displayed a more significant reduction of RQ in response to HFD than LCR, but HFD + BA-Seq lowered RQ in both groups compared with HFD alone, demonstrating a pronounced impact on metabolic flexibility. In conclusion, BA-Seq provides uniform metabolic benefits for metabolic flexibility and adiposity, but rats with higher aerobic capacity display adaptability for hepatic bile acid metabolism.NEW & NOTEWORTHY The administration of bile acid sequestrant (BA-Seq) has uniform metabolic benefits in terms of metabolic flexibility and adiposity in rats with high and low aerobic capacity. However, rats with higher aerobic capacity demonstrate greater adaptability in hepatic bile acid metabolism, resulting in increased fecal bile acid and lipid loss, as well as enhanced fecal energy loss.

Chemical and cell antioxidant activity of amaranth flour and beverage after simulated gastrointestinal digestion. Role of peptides

The potential of peptides generated by simulated gastrointestinal digestion (SGID) of two products derived from Amaranthus manteggazianus seeds, flour (F) and beverage (B), to exert peroxyl scavenging activity (ORAC) and antioxidant action on intestinal cells was studied. B was prepared by solubilisation of seed proteins, with the addition of gums and the application of a pasteurization treatment. The gastrointestinal digests FD and BD showed some differences in the peptide/polypeptide composition. The SGID produced increased ORAC activity for both samples, with some differences in the ORAC of the whole digests BD and FD and of some gel filtration fractions. Bioaccessible fractions (FDdbs and BDdbs) were obtained after treatment with cholestyramine resin to remove bile salts due to their cytotoxicity and oxidative effect. BDdbs presented a greater ORAC potency (IC50: 0.05 ± 0.01 and 0.008 ± 0.004 mg protein/ml for FDdbs and BDdbs, respectively). These fractions showed low cytotoxicity values (measured by LDH release) and produced high intracellular ROS inhibition (around 80 %), increased the SOD activity and the GSH content, with no effect on GPx activity in Caco2-TC7 cells exposed to H2O2. Several fractions with MM < 2.2 kDa presented also these cellular actions; fractions from FD induced higher increases in GSH concentration. Amaranth flour and a processed matrix like the beverage are shown as sources of bioactive peptides with potential cell antioxidant activity.

Cholestyramine resin administration alleviated cerebral ischemic injury in obese mice by improving gut dysbiosis and modulating the bile acid profile

Obesity is a risk factor for cerebrovascular diseases. Accumulating evidence has revealed that gut dysbiosis plays an important role in the pathophysiology of cerebrovascular diseases. However, little is known about the role of gut dysbiosis in stroke in obesity. In this study, we established a rodent middle cerebral artery occlusion (MCAO) model to investigate whether obesity-induced gut dysbiosis exacerbates cerebral ischemic injury and the role of the bile salt sequestrant cholestyramine resin (CR) in gut microbiota and stroke outcome in obese mice. Long-term 45% high-fat diet (HFD) diet (8 weeks) induced an obesity phenotype and caused gut dysbiosis, resulting in a larger infarct volume and higher serum levels of inflammatory cytokines after stroke, compared to those in the lean counterparts. LC-MS/MS and GC analysis revealed that obese mice with stroke developed an obviously perturbed bile acid (BA) profile characterized by higher levels of deoxycholic acid and its conjugated forms, and lower levels of butyrate in the cecal content. CR administration improved the obesity-induced dysbiotic microbiome, attenuated ischemic brain injury and modulated the stroke-perturbed BA profile. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that the impact of obesity on stroke and the neuroprotective effects of CR were mediated by gut microbiota. In conclusion, Obesity induces gut dysbiosis, worsens stroke outcomes, and perturbs the BA profile. The dysbiotic microbiome is an important linkage between obesity and stroke. CR confers metabolic benefits and neuroprotective effects in obesity, perhaps by modulating gut microbial composition and BA metabolism.

The Benevolent Bile: Bile Acids as Stimulants of Liver Regeneration

The Benevolent Bile: Bile Acids as Stimulants of Liver Regeneration

Sitosterolemia (phytosterolemia)

Sitosterolemia or phytosterolemia is arare autosomal recessive hereditary lipid storage disorder. It is caused by homozygous or compound heterozygous mutations in one of the two ABCG5 and ABCG8 genes encoding the intestinal and hepatic heterodimer ABCG5 (sterolin 1)/ABCG8 (sterolin 2) efflux transporters. These mutations lead to intestinal hyperabsorption and reduced hepatic secretion of cholesterol and plant sterols with subsequent accumulation of phytosterols and cholesterol in plasma and deposition in tissue (xanthoma). Phytosterols are found mainly in vegetable oils, margarine, nuts, grains, soybeans and avocados. Patients with sitosterolemia show extreme phenotypic heterogeneity from almost asymptomatic individuals to those with combined severe hypercholesterolemia at ayoung age, leading to increased atherosclerosis and premature cardiac death. Early abnormalities include hemolytic anemia with stomatocytosis, macrothrombocytopenia and splenomegaly. In addition to strict avoidance of phytosterol-containing foods, the use of the sterol absorption inhibitor ezetimibe, possibly in combination with the bile acid-binding resin cholestyramine, is the most effective treatment option.

TcpP L152A Constitutively Activating Virulence Gene Expression in Vibrio cholerae.

Vibrio cholerae, the causative agent of severe watery diarrheal disease cholera, requires production of a number of virulence factors during infection which results from the activity of a cascading system of regulatory factors by sensing to different environmental signals. TcpP, a membrane-localized transcription activator in V. cholerae, activates virulence factors production by responding to human host signals. To better characterize the transmembrane helix in regard to its roles on TcpP positive effectors sensitivity, site-directed mutagenesis was performed to identify specific mutations in this region which could enhance TcpP transcription activity in the absence of stimuli, like bile salts. We found that TcpP L152A constitutively forms homodimer and activates toxT expression in the absence of bile salts. However, being active, TcpP L152A needs to form disulfide bonds between the cysteine residues in the periplasmic domain of TcpP. We also found that TcpP L152A showed a competitive advantage in the infant mouse colonization model by coadministrating the bile salt-sequestering resin cholestyramine. All these results demonstrate that the transmembrane helix of TcpP plays an important role in regulating TcpP transcription activity in response to its positive effectors.

The Role of Bile Acid Sequestrant in Diarrhea Management: Too Good to Be True?

Background: diarrhea can be caused by a wide range of conditions including malabsorption (e.g. Bile acid malabsorption (BAM)), infection (eg. Clostridium difficile (C. difficile)), other gastrointestinal diseases (e.g. ileal resection, bile acid overproduction, pancreatic insufficiency, bacterial overgrowth, cholecystectomy and malignancy), and even stress and anxiety. BAM is a condition associated with inability to effectively absorb bile in the small intestine which results in chronic diarrhea. is a bile acid sequestrant (BAS) with the potential to control chronic diarrhea induced by BAM and C. difficile infection. Objective: To explore the role of BAS in the management of chronic diarrhea and assess how the theoretical knowledge is supported by practical evidence. Methods: Ovid (MEDLINE, PsychInfo, Embase) was searched for Cholestyramine Resin” AND Chronic Diarrhea with limits on the years 1946 – present. 8 studies which were deemed to be relevant to the objective at hand were summarized. Additional sources from Grey literature search were added using the same research strategies. Results: The results showed positive therapeutic impact of BAS, particularly cholestyramine in reducing stool frequency regardless of type and severity of BAM-induced diarrhea. However, low tolerability of BAS due to adverse effects can limit its use in some patients. Conclusion: BAS was more likely to be a good option as a short-term medication to better control symptoms and prevent illness. Therapeutic effect of BAS in the management of chronic diarrhea can be considered in palliative care to benefit patients who can tolerate this medication although not without the existent controversies.

Combined efficacy of Vigna radiata (L.) R. Wilczek and Amorphophallus paeoniifolius (Dennst.) Nicolson on serum lipids in albino rats.

Coronary Artery Disease (CAD) is a major killer disease throughout the world. Dyslipidemia is a major contributor to the risk of CAD. Several dietary articles traditionally used in India and other South Asian countries reduced dyslipidemia. The present study was undertaken to evaluate the combined effect of Mung bean (Vigna radiata) and Elephant foot yam (Amorphophallus paeoniifolius) on serum lipids and atherogenic indices in albino rats and to compare it with a standard drug Cholestyramine. Thirty healthy albino rats of both sexes (150–200 g) were randomized to 5 groups of 6 animals each. The grouping were done based on the following criteria: Group I: Normal Control Group, Group II: (Standard Group): Cholestyramine resin 5 mg/kg bw, Group III: (Half Dose Group): Drug powder at 540 mg/kg bw, Group IV: (Effective Dose Group): Drug powder at 1080 mg/kg bw, and Group V: (Double Dose Group): Drug powder at 2160 mg/kg bw. Lipid profile was estimated at the beginning and after 30 days of treatment. The Effective and Double doses of the drug reduced Total cholesterol along with levels of Triglycerides, Low density lipoprotein and Very low density lipoprotein levels significantly (p < 0.01) along with a significant (p < 0.01) increase in high density lipoproteins (HDL) in rats. There was also significant (p < 0.01) improvement in atherogenic indices like Castelli Risk Index I, Non HDL C/HDL, Castelli risk Index II, TG/HDL, Atherogenic coefficient and Atherogenic Index of Plasma. The combination of powdered sprouted mung bean and yam powder have excellent lipid lowering potential.

PRURITUS IN CHRONIC CHOLESTATIC LIVER DISEASES

Pruritus can be a prominent symptom in patients with chronic liver disorders, especially those with cholestasis, and substantially affects quality of life. Management of pruritus in cholestatic liver diseases remains a complicated medical problem. The review article deals with pathophysiological mechanisms of pruritus in cholestatic liver diseases, in particular, with the role of bile acids, endogenous opioids, serotonin, and histamine. There is new data on the key pathophysiological elements, such as neuronal activation lysophosphatidic acid and autotaxin, an enzyme that produces lysophosphatidic acid and whose serum activity is associated with the intensity of pruritus. Pathophysiology-based management approaches include administration of anionic exchange resin cholestyramine, ursodeoxycholic acid, rifampicin agonists, an opioid antagonist naltrexone and a serotonin-reuptake inhibitor sertraline. These agents are recommended for the use as a stepped treatment algorithm. Patients who do not respond to these therapies can become candidates for albumin dialysis, plasmapheresis, ultraviolet B phototherapy, or need some other individualized approaches. New knowledge on the pathophysiology of pruritus may potentially result in the development of new agents for cholestatic pruritus.

Cholestyramine as a promising, strong anion exchange resin for direct capture of genetic biomarkers from raw pancreatic fluids.

The ability to capture cell-free DNA from the gastrointestinal tract, in a minimally invasive manner, could enhance our ability to diagnose gastrointestinal disease, or gain a better understanding of the spatial mapping of the intestinal microbiota. We, therefore, sought to identify a class of capture agents that could directly and efficiently sequester genetic material from intestinal fluids. As a particular case study, we examined the ability to capture DNA from pancreatic secretions, for potential application in enabling the sequestration of early, genetic biomarkers of pancreatic disease. We hypothesized that the cholestyramine series of strong cation exchange resins, which are FDA approved for the treatment of high cholesterol, may be capable of capturing DNA from pancreatic secretions. We identified a particular cholestyramine resin, DOWEX 1 × 2 100-200 mesh, which is able to efficiently capture and purify DNA from pancreatic fluid. Using only 200 μL of pancreatic secretions, we are able to recover 247 ± 182 ng of amplifiable human DNA, giving an estimated pancreatic fluid DNA content of 1.23 ± 0.91 ng/μL. To our knowledge, this is the first demonstration of a material that can effectively capture and purify DNA directly from untreated pancreatic fluids. Thus, our approach could hold high utility for the in vivo capture of DNA and disease biomarkers if incorporated into an appropriate sampling device. Biotechnol. Bioeng. 2017;114: 934-938. © 2016 Wiley Periodicals, Inc.

Screening bioactive components affecting the capacity of bile acid binding and pancreatic lipase inhibitory activity

The hypothesis of the current study was that bioactive components including vitamins, dietary fibers, and polyphenols may have both the ability to bind to bile acid and inhibit pancreatic lipase activity. s-carotene, vitamin C, and vitamin U as vitamin, cellulose, s-glucan, and pectin as dietary fibers, and apigenin, curcumin, hesperidin, kaempferol, and quercetin as polyphenols were chosen. The bile acid binding capacity was measured via the furfural–H2SO4 test at the concentration of 2.5 mg/mL with cholestyramine resin used as a positive control (binding value of 87.17 %). The pancreatic lipase inhibitory ability of bioactive components was measured by following the hydrolysis of p-nitrophenyl butyrate. Among the compounds tested, pectin, vitamin C, and s-glucan had the highest binding capacity to bile acid, at 82.7, 67.8, and 33 %, respectively. The results suggest a positive correlation between water solubility and the bile acid binding capacity of the tested bioactive components. At 20 mg/mL concentration, the inhibiting values of all components were relatively lower than the positive control (orlistat, 54.4 %), ranging from 1.3 to 7.6 % of the negative control. Among them, curcumin and cellulose are the highest pancreatic lipase inhibitors with inhibiting values of 7.6 and 7.5 %, respectively. These results imply s-glucan, pectin, vitamin C, cellulose, and curcumin as potential components in reducing the uptake of hydrophobic toxic components through inhibiting micelle formation under human digestion fluid.

Cholestatic Itch Management.

Cholestatic itch is a feature of numerous hepatobiliary disorders such as primary biliary cirrhosis, primary sclerosing cholangitis, the inherited form of cholestasis, and intrahepatic cholestasis of pregnancy. Although undervalued by physicians, cholestatic itch can be a source of great discomfort to the patient and significantly affects quality of life. Many pruritogens such as bile salts, opioids, serotonin, and histamine have been implicated in the pathogenesis of cholestatic itch, but no causative link has ever been established. Recent findings indicate that the potent neuronal activator lysophosphatidic acid and autotaxin, the enzyme forming lysophosphatidic acid, may be key elements in its pathogenesis. Treatment options for patients with cholestatic itch include the anion exchange resin cholestyramine, bile acid ursodeoxycholic acid, PXR agonist rifampicin, opioid antagonist naltrexone, and the serotonin inhibitor sertraline. These drugs can be used as a stepwise therapeutic approach. The body of evidence for many of these options, however, is not very robust. Patients who do not respond to medical therapy can be candidates for interventional measures, such as albumin dialysis, plasmapheresis, or nasobiliary drainage, or certain experimental approaches such as UVB phototherapy. Research over the past decade has elucidated many of the receptors and neuropeptides involved in itch sensation and transmission; it is hoped that in the future this will lead to the development of novel antipruritic medication for cholestatic itch.

Co‐administration of a Grape Seed Procyanidin Extract and the Bile Acid Sequestrant, Cholestyramine, Results in Beneficial Metabolic Alterations, Including Decreased Triglyceride Levels

Bile acid (BA) sequestrants, used to lower cholesterol levels, may be taken alone or in combination with cholesterol‐lowering medication. We previously showed that grape seed procyanidin extract (GSPE) reduces enterohepatic BA recirculation as a new mechanism to reduce serum triglyceride (TG) levels. This study aimed to determine the effects of co‐administering an acute dose of GSPE with the BA‐binding resin cholestyramine (CHY) on TG levels and BA homeostatic gene expression.&#x0D; Eight‐week old C57BL/6 mice were treated for 4 weeks with a control diet, or a 2% CHY‐supplemented diet, after which, they were administered vehicle or GSPE (250mg/kg) for 14 hours. Tissues were harvested and gene expression levels were analyzed via qPCR. Biochemical analysis was performed to assess serum BA and TG levels. Data were analyzed using one‐way ANOVA.&#x0D; Results show that CHY‐GSPE co‐administration reduces intestinal IBABP (61%, p&lt;0.0001) and FGF15 (99.5%, p&lt;0.0001) expression, relative to control. In addition serum BA levels were decreased 74% (p&lt;0.0001), while hepatic CYP7A1 expression was increased 13‐fold (p&lt;0.0001), indicative of increased BA synthesis. SREBP1c expression was reduced 42% and serum TG levels were decreased 34% in the CHY‐GSPE group, compared to control.&#x0D; We present novel evidence showing that GSPE works synergistically with CHY to lower serum TG levels, which is achieved via enhanced de novo BA biosynthesis.

Development and in vitro characterization of a multiparticulate delivery system for acyclovir-resinate complex

Context: Herpes viruses cause threatening infections in humans and stand second as causative agents for most human viral diseases, after influenza and cold viruses. Objective: A novel multiparticulate delivery system for acyclovir (ACV), based on ion-exchange resin, was developed to achieve a gastro-mucoadhesive effect in order to effectively combat the herpes simplex virus. Materials and methods: A combination of ACV and cholestyramine resin was optimized and further entrapped within sodium alginate and Carbopol microbeads. The developed systems were evaluated for drug entrapment efficiency (DEE), percentage of mucoadhesion, and in vitro release characteristics in simulated gastric fluid (SGF, pH 1.2). Results: With the aid of scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR), the interaction of the resinate and polycations with alginate has been revealed, which consequently supports the formation of the membrane by the polyelectrolyte complex. The in vitro drug release studies demonstrate that formulations without the drug-resin complex (DRC) released the drug more rapidly than formulations containing DRC, which released the drug in a controlled manner, due the formation of a complex between drug and resin. Discussion and conclusion: Preliminary results from this study suggest that these DRC-entrapped microbeads may be used to incorporate other antiviral drugs and could be effective against infections caused by herpes viruses. Such formulations developed could be subjected to in vivo studies in future, in order to prove complete clearance of herpes infections.

Delivery of Repaglinide-Cholestyramine Complex Loaded Ethylcellulose Microspheres to Gastric Mucosa for Effective Management of Type-2 Diabetes Mellitus

The main aim of this work is to develop and thoroughly evaluate resin-based multiparticles of repaglinide for effective management of type-2 diabetes mellitus. Repaglinide was complexed with cholestyramine resin; later the resin complexed drug was encapsulated in ethylcellulose microspheres. The microspheres were characterized for micromeritic properties, SEM analysis, entrapment efficiency, percentage yield, IR spectroscopy, buoyancy behaviour and in vitro drug release in simulated gastric fluid. Microparticles showed regular shape and spherical morphology with entrapment efficiency in the range 51-69%. Differential scanning calorimetry confirmed that there was no chemical interaction between the polymer and the drug. Resin-based microspheres showed good buoyancy behaviour (P < 0.05) due to the presence of bicarbonate ions and sustained release compared to plain drug microspheres (P < 0.05). Finally, the effectiveness of the formulations was evaluated in vivo for blood glucose lowering effect in both normal and streptozotocin-induced diabetic rats. Blood glucose lowering effect induced in diabetic rats by the repaglinide- loaded microspheres was significantly greater (P < 0.05) and prolonged (∼8 h) compared to plain drug microspheres. In a nutshell, floating microspheres containing drug resin complex were able to sustain the drug release in an effective manner for prolonged periods of time and proven in vivo effectiveness by reducing blood glucose level for a longer duration.

Very Long O-antigen Chains Enhance Fitness during Salmonella-induced Colitis by Increasing Bile Resistance

Intestinal inflammation changes the luminal habitat for microbes through mechanisms that have not been fully resolved. We noticed that the FepE regulator of very long O-antigen chain assembly in the enteric pathogen Salmonella enterica serotype Typhimurium (S. Typhimurium) conferred a luminal fitness advantage in the mouse colitis model. However, a fepE mutant was not defective for survival in tissue, resistance to complement or resistance to polymyxin B. We performed metabolite profiling to identify changes in the luminal habitat that accompany S. Typhimurium-induced colitis. This analysis suggested that S. Typhimurium-induced colitis increased the luminal concentrations of total bile acids. A mutation in fepE significantly reduced the minimal inhibitory concentration (MIC) of S. Typhimurium for bile acids in vitro. Oral administration of the bile acid sequestrant cholestyramine resin lowered the concentrations of total bile acids in colon contents during S. Typhimurium infection and significantly reduced the luminal fitness advantage conferred by the fepE gene in the mouse colitis model. Collectively, these data suggested that very long O-antigen chains function in bile acid resistance of S. Typhimurium, a property conferring a fitness advantage during luminal growth in the inflamed intestine.

Tratamiento de la hipercolesterolemia y prevención de las enfermedades cardiovasculares mediante la inhibición de la reabsorción de ácidos biliares con resincolestiramina

Cholestyramine resin is a bile acid sequestrant that reduces low-density-lipoprotein cholesterol (LDL-c) through partial interruption of enterohepatic bile acid circulation. This drug has no systemic effects and consequently can be used in women of reproductive age, in children and in patients with muscular, liver or renal disorders. Cholestyramine resin should be administered separately from other drugs. This agent boosts the lipidlowering effect of statins, as well as that of fibrates, nicotinic acid and ezetimibe. Adding cholestyramine resin to statin therapy reduces LDL-c by an additional 20%, equivalent to a 3-fold increase in the statin dose. A meta-analysis of eight clinical trials found that resins reduced mortality from cardiac causes by 30% (OR 0.70; 95% CI 0.50–0.99), a figure not lower than that observed with statins. Cholestyramine resin reduces postprandial glycemia and glycosylated hemoglobin and consequently is of particular interest in the treatment of hypercholesterolemia in patients with metabolic syndrome or type 2 diabetes who have failed to achieve LDL-c targets with statin monotherapy. Previously used resin preparations often produced gastrointestinal intolerance, while the new galenical preparations of cholestyramine resin used at a dose of 4–8 grams (1–2 sachets) per day – sufficient to obtain a lipid-lowering effect – are usually well tolerated.

Measurement of 75Se-SeHCAT Abdominal Retention in the Initial Diagnosis of Bile Acid Absorption (BAM)

Aim To evaluate the usefulness of the 75SeHCAT abdominal retention (AR) measurement in the early diagnosis of diarrhea syndrome (DS). Methods Thirty-seven patients with diarrhea syndrome within the first month of evolution were prospectively evaluated. The 75Se-SeHCAT abdominal retention was measured 4 and 7 days post-administration of 0.01 mCi of 75SeHCAT. The test was performed prior to treatment and at 3 months when the baseline study was positive. The test was considered positive if the RA was <25% at 4th and <10% on the 7th day. The patients were followed up at 3 months. Depending on the response, 3 groups were established: (a) complete response: normalization of stool frequency, (b) partial response, decrease of frequency and (c) no response. Results Group A: The AR of 75Se-SEHCAT was normal in 21 patients. Six were diagnosed of colonic diverticulosis, 8 of irritable bowel syndrome, 1 of lymphocytic colitis, 1 of post-gastroenteritis syndrome, 1 of celiac disease and 1 of stenosis of the cardia. Four are still under study. Group B: The AR of 75Se-SEHCAT decreased in 16 patients. All showed abnormal AR at day 7 and all but 1 at day 4. Following administration of cholestyramine resin, 8 (50%) presented partial response and 8 presented (50%) complete response. At 3 months, AR had increased at day 4 and 9 at day 7. Conclusion The measurement of 75SEHCAT abdominal retention allows the early diagnosis of bile acid malabsorption in 43% of the patients with DS. Measurement at 7 days seems more accurate than that at 4 days.