Short Bowel Syndrome
John K. DiBaise, Carol Rees Parrish, Jon S. Thompson in Short Bowel Syndrome Practical Approach to Management, 2017
The enterohepatic circulation is important for the action of some drugs such as loperamide, which enter this circulation, and, if disrupted by ileal resection, bypass, or disease, higher than normal doses of loperamide are needed to achieve the same effect. Unabsorbed bile acids within the colon (e.g., after an ileal resection) stimulate salt and water secretion and motility, thereby worsening diarrhea. A bile acid sequestrant may occasionally be beneficial; however, in the setting of short bowel, there is often bile acid deficiency, and use of a bile acid sequestrant will only worsen fat malabsorption and steatorrhea. Conjugated bile acid replacement therapy (e.g., cholylsarco-sine) has been used to improve fat absorption in patients with a short bowel but is not widely available [52–53].
Binders in Pharmaceutical Granulation
Dilip M. Parikh in Handbook of Pharmaceutical Granulation Technology, 2021
Pregelatinized starch is classified as modified starch. Chemical and mechanical treatment is used to rupture all or part of the native starch granules. Pre-gelatinization enhances starch cold-water solubility and also improves compactibility and flowability. PGS is marketed as a multifunctional excipient, providing binding, disintegration, good flow, and lubrication. PGS monographs can be found in the United States Pharmacopeia/National Formulary (USP/NF), European Pharmacopeia (Ph. Eur.), and JPE [15]. It is typically used from solution in wet granulation; it can also be dry added, but this reduces efficiency significantly. Furthermore, at 15% to 20%, use levels are usually higher for PGS relative to other binders. PGS is not compatible with organic solvents and thus is used only in aqueous binder systems. While it tends to have high equilibrium moisture levels (Figure 4.2), starch is known to hold water in different states, that is, only a portion of the sorbed water will be available as “free” water. This property can be exploited by using starch as a stabilizer or moisture sequestrant. Partially pregelatinized starch is the most frequently used form of PGS, but fully pregelatinized starch is also available. The degree of pre-gelatinization determines cold water solubility. Commercial partially pregelatinized starch typically has around 20% pregelatinized or water-soluble content. The cold-water soluble part acts as a binder, while the remainder aids tablet disintegration. For this reason, fully pregelatinized starches tend to have higher binder efficiency, but not necessarily good disintegrant properties.
Microbial environment of the manufacturing plant
Philip A. Geis in Cosmetic Microbiology, 2006
Chelating agents are organic sequestering agents that inactivate water hardness and other metallic ions in water. A commonly used chelating agent is EDTA (ethylene diamine tetraacetic acid and its salts). A sequestrant is a chelating compound in an aqueous solution that combines with a metallic ion to form a water-soluble combination. The ion in the combination is inactive. Sequestrants soften water without the precipitation associated with other methods like lime softening. For example, complex phosphates are sequestrants that inactivate divalent metal ions such as calcium, magnesium, iron, and manganese without precipitation.
Preclinical discovery and development of colesevelam for the treatment of type 2 diabetes
Published in Expert Opinion on Drug Discovery, 2018
Henriette Holst Nerild, Mikkel Bring Christensen, Filip Krag Knop, Andreas Brønden
In 2000 and 2004, the FDA and EMA, respectively, approved the bile acid sequestrant (BAS) colesevelam for the treatment of hyperlipidemia, as monotherapy as well as in combination with other lipid-lowering drugs. BASs are a well-described class of cholesterol-lowering drugs and have been used for this indication for more than 35 years. Treatment with the first-generation BAS, cholestyramine has been shown to contribute to a reduction in both the risk and progression of CVD [11,12]. The second-generation BAS, colesevelam holds greater specificity, affinity and binding capacity for bile acids compared with the first-generation BASs (cholestyramine and colestipol) [13], and clinical studies have demonstrated colesevelam monotherapy to reduce LDL cholesterol by 15–19% [14,15]. Moreover, colesevelam is considered a safe add-on treatment to statin therapy in patients with an additional need for LDL cholesterol-lowering [16,17].
Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives
Published in Expert Opinion on Investigational Drugs, 2018
Enrique Soto-Perez-De-Celis, Kah Poh Loh, Capucine Baldini, Nicolò Matteo Luca Battisti, Yanin Chavarri-Guerra, Nienke A. De Glas, Tina Hsu, Arti Hurria
In summary, the evidence regarding the use of neratinib in older adults is very limited, and less than 15% of patients included in clinical trials were aged ≥65 [78,81]. Importantly, a meta-analysis found that the incidence of all-grade diarrhea in neratinib trials was 89% [82]. Therefore, antidiarrheal prophylaxis with loperamide is recommended starting with the first dose of neratinib and continuing for two cycles [81]. An ongoing phase II trial (NCT02673398) will help to estimate the safety and tolerability of neratinib in older adults with metastatic BC, and to understand if geriatric assessments can adequately identify patients who may better tolerate treatment. Additionally, at least two phase II studies are evaluating strategies to ameliorate neratinib-associated diarrhea, such as the use of the chloride channel-blocker crofelemer (NCT03094052), the bile acid sequestrant colestipol, and budesonide (NCT02400476).
Mechanism of Asbt (Slc10a2)-related bile acid malabsorption in diarrhea after pelvic radiation
Published in International Journal of Radiation Biology, 2020
Lina Wang, Yan Zhou, Xiaohu Wang, Guangwen Zhang, Bin Guo, Xiaoming Hou, Juntao Ran, Qiuning Zhang, Chengcheng Li, Xueshan Zhao, Yichao Geng, Shuangwu Feng
Cholestyramine, a type of BA sequestrant, was administered to sequester the excessive BAs. As shown in Figure 7(A), the body weight of rats was significantly decreased after pelvic radiotherapy (p < .01, p < .05). The situation did not improve after the administration of cholestyramine. However, as shown in Figure 7(B), the degree of diarrhea caused by pelvic irradiation was significantly ameliorated by the administration of cholestyramine after irradiation. It was shown that diarrhea occurring after pelvic irradiation was related to the increased excretion of BAs.
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