Article
Obstetrics & Gynecology
Gary Peltz, Lauren M. Jansson, Susan Adeniyi-Jones, Carol Cohane, David Drover, Steven Shafer, Meiyue Wang, Manhong Wu, Balaji Govindaswami, Priya Jegatheesan, Cynthia Argani, Salwa Khan, Walter K. Kraft
Summary: Ondansetron treatment reduces the severity of symptoms in neonatal opioid withdrawal syndrome (NOWS) and may indicate a shortened length of stay.
JOURNAL OF PERINATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rong Li, Sheng Xu, Bei Li, Bo Zhang, Weihua Chen, Die Dai, Zhi Liu
Summary: Refractory constipation is a severe form of constipation with unknown etiology. Accumulating studies have shown significant dysbiosis of the gut microbiota in constipation patients. This study analyzed the gut microbiota composition of fresh and accumulated feces of refractory constipation patients and found a significant difference between them.
Article
Food Science & Technology
Wei-Feng Cai, Song-Xia Lin, Pan-Yu Ma, Chun-Yan Shen
Summary: This study demonstrates that Semen Pruni oil can treat constipation by regulating neurotransmitters, oxidative stress, and inflammatory responses to alleviate constipation symptoms.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Review
Clinical Neurology
Ying-Ying Zhang, Rong Zhou, Wan-Jie Gu
Summary: The meta-analysis results indicate that methylnaltrexone is effective and safe in alleviating opioid-induced constipation, but caution should be taken regarding the safety of abdominal pain.
Article
Chemistry, Applied
Juqing Huang, Bin Lin, Ying Zhang, Zhenglu Xie, Yi Zheng, Qi Wang, Hang Xiao
Summary: BSH-1 demonstrated protective effects against Lop-induced constipation in mice by regulating defecation time, gastrointestinal transit rate, stool production, cecal SCFAs concentration, gut hormones and neurotransmitters levels, cecal microbiota composition, and colonic gene expression related to intestinal motility, water and ion transport, inflammation, and cancer.
CARBOHYDRATE POLYMERS
(2022)
Article
Oncology
Darren M. Brenner, Neal E. Slatkin, Nancy Stambler, Robert J. Israel, Paul H. Coluzzi
Summary: This study investigated whether brain metastases in cancer patients receiving MNTX for OIC compromise the central effects of opioids. The results showed that focal disruptions of the BBB caused by brain metastases did not alter the central nervous system penetrance of MNTX, and MNTX significantly alleviated constipation symptoms within 4 hours.
SUPPORTIVE CARE IN CANCER
(2021)
Article
Biochemistry & Molecular Biology
Ziqi Wang, Yali Shi, Shiyu Zeng, Yuanping Zheng, Huaijie Wang, Haihui Liao, Jie Song, Xinyue Zhang, Jun Cao, Chuan Li
Summary: This study investigated the regulatory effects of Holothuria leucospilota polysaccharides (HLP), a bioactive component of marine resources, on loperamide-induced constipation. HLP treatment improved constipation symptoms, enhanced water-electrolyte metabolism, and increased gastrointestinal motility in constipated mice. The treatment also reduced intestinal barrier damage, inhibited inflammatory response, and improved the composition of intestinal microbiota, leading to increased production of short-chain fatty acids (SCFAs) in the intestine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Food Science & Technology
Wenhui Liu, Aimin Zhi
Summary: The study investigated the protective effects of Quercetin against loperamide-induced constipation in rats, finding that Quercetin could improve intestinal transit rate, motilin levels, gastrin levels, substance P levels, SCFAs concentration, and gastrointestinal peristalsis. Quercetin also increased the levels of interstitial cells of Cajal markers and aquaporin 3.
FOOD SCIENCE & NUTRITION
(2021)
Article
Plant Sciences
Tian Li, Mengmeng Hu, Cuihua Jiang, Dongjian Zhang, Meng Gao, Jianwei Xia, Mengqi Miao, Gaofeng Shi, Hui Li, Jian Zhang, Zhiqi Yin
Summary: The study aimed to elucidate the potential laxative mechanisms of Tiantian capsule in loperamide-induced constipated rats. Results showed that TTC attenuated constipation responses, restored neurotransmitter levels, and increased the thickness of the mucus layer. The laxative effect of TTC is likely due to the regulation of bowel movement and intestinal fluid secretion.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Rong Li, Min Li, Bei Li, Wei-Hua Chen, Zhi Liu
Summary: This study found that the water extract of Cannabis sativa L. has a laxative effect and improves intestinal motility and water-electrolyte metabolism. It also reduces inflammatory responses, prevents gut barrier damage, and relieves anxiety and depression symptoms in constipated mice. Furthermore, it structurally remodels the gut microbiota and alters the abundance of bacteria related to inflammation. The research suggests that the effects of Cannabis sativa L. on constipation symptoms depend on the gut microbiota.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Nutrition & Dietetics
Buyu Liu, Zhiguo Zhang, Xingquan Liu, Weiwei Hu, Weicheng Wu
Summary: The study investigated the role of gastrointestinal polysaccharide fermentation in alleviating constipation. Two polysaccharide fractions were isolated and tested in mice. The results showed that the neutral polysaccharide fraction improved GI transit rate and showed better fermentation properties compared to the acidic fraction. This suggests that neutral polysaccharides could be beneficial in alleviating constipation.
Article
Microbiology
Jin-Ju Jeong, Raja Ganesan, Yoo-Jeong Jin, Hee Jin Park, Byeong Hyun Min, Min Kyo Jeong, Sang Jun Yoon, Mi Ran Choi, Jieun Choi, Ji Hyun Moon, Uigi Min, Jong-Hyun Lim, Do Yup Lee, Sang Hak Han, Young Lim Ham, Byung-Yong Kim, Ki Tae Suk
Summary: This study evaluated the effect of intragastric administration of probiotics on loperamide-induced constipation in rats. The multi-strain probiotics significantly increased the number of fecal pellets and improved gastrointestinal transit rate. The mRNA expression levels of serotonin- and mucin-related genes in the treated colons were significantly increased. Short-chain fatty acids, serotonin, and mucin levels were altered through improvement in intestinal microflora.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Nutrition & Dietetics
Bo Qiu, Lian Zhu, Shuobo Zhang, Shengyi Han, Yiqiu Fei, Furong Ba, Bjorn Berglund, Lanjuan Li, Mingfei Yao
Summary: In this study, the potential of Ligilactobacillus salivarius Li01 in alleviating constipation was investigated. The results showed that Li01 can relieve constipation symptoms by improving fecal characteristics, modulating gut motility, and altering gut microbiota composition.
Article
Biochemistry & Molecular Biology
Ji-Eun Kim, Yun-Ju Choi, Su-Jin Lee, Jeong-Eun Gong, You-Jung Jin, So-Hae Park, Hee-Seob Lee, Young-Whan Choi, Jin-Tae Hong, Dae-Youn Hwang
Summary: This study demonstrated that exposure to Pt improves the constipation phenotype in SD rats with Lop-induced constipation by regulating membrane water channel expression, GI hormones, the mAChR signaling pathway, and fecal microbiota.
Article
Environmental Sciences
Meng Xu, Wenjuan Wang, Shunyong Su, Wanggao Li, Xiaosong Hu, Jiachao Zhang
Summary: This study aimed to investigate the effects and mechanism of arecoline in relieving constipation. The results showed that arecoline can alleviate constipation by improving intestinal transit time, increasing fecal water content, improving small bowel propulsion, and increasing defecation frequency. In addition, arecoline can regulate gut microbial composition, metabolites, and gene expression related to intestinal diseases.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Chemistry, Medicinal
Katharina Krollik, Andreas Lehmann, Christian Wagner, Jonathan Kaidas, Janina Buelhoff, Holger Kubas, Werner Weitschies
Summary: Biopharmaceutical precipitation assays are important for studying the precipitation behavior of weakly basic drugs during their transit from the stomach into the small intestine. This study evaluated the stability of FaSSIF under different storage conditions and investigated the impact of stressed FaSSIF on the supersaturation and precipitation behavior of ketoconazole. The results showed that the composition of FaSSIF changed during storage, which affected the supersaturation and precipitation behavior of ketoconazole in in vitro transfer studies.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Medicine, Research & Experimental
Adrian Rump, Carolin Tetyczka, Eva Littringer, Marie-Luise Kromrey, Robin Buelow, Eva Roblegg, Werner Weitschies, Michael Grimm
Summary: Gastroretentive dosage forms, which can release drugs inside the stomach for a prolonged period, offer advantages such as improved pharmacokinetics/bioavailability and reduced intake frequency, leading to better patient adherence. However, there are currently no gastroretentive products with proven efficacy in humans. One effective approach is the use of mucoadhesive properties to prevent gastric emptying. The adhesion time of minitablets containing Carbopol 71G NF was significantly longer compared to non-adhesive minitablets, resulting in delayed gastric emptying. However, further improvement is needed to achieve clinical benefits, and variations in gastric residence time were observed.
MOLECULAR PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Michael Grimm, Adrian Rump, Lisa Meilicke, Maximilian Feldmueller, Rebecca Kessler, Eberhard Scheuch, Mladen Vassilev Tzvetkov, Werner Weitschies
Summary: Gastric water emptying, which is important for oral drug absorption, can be investigated using imaging techniques or pharmacokinetic interpretation. This study compared the salivary caffeine pharmacokinetics of naturally occurring C-12-caffeine and stable isotope-labeled C-13(3)-caffeine for evaluating gastric emptying. The results showed congruence and good linear correlations between the two caffeine species, indicating that the substitution of natural C-12 caffeine with stable isotope-labeled C-13(3)-caffeine can broaden the application of the salivary caffeine gastric emptying technique and improve its robustness against environmental contamination.
Article
Pharmacology & Pharmacy
Michael Grimm, Philipp Aude, Maximilian Feldmueller, Rebecca Kessler, Eberhard Scheuch, Mladen V. Tzvetkov, Mirko Koziolek, Werner Weitschies
Summary: Gastrointestinal fluid volumes are crucial for dissolution and absorption of orally taken medications. However, survey results show that the actual intake of oral medications is much lower than the clinical standard. This study aimed to compare the gastric emptying of 240 mL and 20 mL of water in healthy volunteers. The results showed that the absolute gastric volumes differed significantly but relative gastric emptying was similar. The reduced fluid volumes might interfere with dissolution and absorption.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Nutrition & Dietetics
Stefan Senekowitsch, Eliza Wietkamp, Michael Grimm, Franziska Schmelter, Philipp Schick, Anna Kordowski, Christian Sina, Hans Otzen, Werner Weitschies, Martin Smollich
Summary: This study investigated the pharmacokinetics of oral spermidine supplementation for the first time, and found that spermidine supplementation significantly increased plasma spermine levels, while it did not affect spermidine or putrescine levels. This suggests that dietary spermidine is converted into spermine and contributes to the in vitro and clinical effects of spermidine.
Article
Pharmacology & Pharmacy
Hannes Gierke, Susan Mouchantat, Sabine Berg, Michael Grimm, Stefan Hadlich, Marie-Luise Kromrey, Thomas Nolte, Teresa Pfrommer, Vincent Roennpagel, Adrian Rump, Kerstin Schaefer, Ann-Cathrin Willmann, Werner Weitschies
Summary: Spray-dried amorphous solid dispersions of new chemical entities and pH-dependent soluble polymer hydroxypropyl methylcellulose acetate succinate (HPMC-AS) formed solid agglomerates in the gastrointestinal tract of rodents, termed pharmacobezoars, which posed a potential risk for animal welfare. In this study, we investigated the use of viscosity enhancement of the vehicle to reduce the formation of pharmacobezoars after repeated daily oral dosing to rats. The results showed that viscosity enhancement reduced the incidence, delayed the onset, and decreased the mass of pharmacobezoars.
Article
Pharmacology & Pharmacy
Henriette Hummler, Cordula Stillhart, Lisa Meilicke, Michael Grimm, Elischa Krause, Marwan Mannaa, Maik Gollasch, Werner Weitschies, Susanne Page
Summary: Older adults are the main recipients of oral medications due to their high prevalence of multiple diseases. Patient-centric drug products with high acceptability are needed to ensure successful pharmacological treatment. However, there is limited knowledge on the appropriate size and shape of solid oral dosage forms, especially in older adults. A randomized intervention study involving older and young adults was conducted to compare the swallowability of different coated placebo tablets with varying weights and shapes. Swallowability was assessed using a questionnaire-based method, and the results showed that all tested tablets were swallowed by >= 80% of adults, regardless of age. However, only the 250 mg oval tablet was considered easily swallowable by >= 80% of older participants. Young participants also found the 250 mg round and 500 mg oval tablets easily swallowable. Additionally, swallowability was found to influence the willingness to take tablets on a daily basis, especially over longer periods of time.
Article
Pharmacology & Pharmacy
Laura Mueller, Christoph Rosenbaum, Adrian Rump, Michael Grimm, Friederike Klammt, Annabel Kleinwort, Alexandra Busemann, Werner Weitschies
Summary: The absorption of drugs with narrow absorption windows in the upper small intestine can be enhanced with a mucoadhesive drug delivery system. To predict the mucoadhesive behavior, suitable in vitro or ex vivo methods can be used. This study investigated the influence of tissue storage and sampling site on the mucoadhesion of polyvinyl alcohol film to human small intestinal mucosa. Initial results suggest that adhesion to porcine and human mucosa are equivalent.
Article
Pharmacology & Pharmacy
Stefan Senekowitsch, Constantin Foja, Toni Wildgrube, Philipp Schick, Christoph Rosenbaum, Julius Krause, Friederike Brokmann, Marie-Luise Kromrey, Stefan Engeli, Werner Weitschies, Michael Grimm
Summary: Sparkling water was hypothesized to increase gastric motility and potentially affect drug absorption due to the release of carbon dioxide. In a crossover study with twelve healthy volunteers, the salivary caffeine pharmacokinetics were compared after administration of effervescent and non-effervescent granules with still and sparkling water. The administration of effervescent granules with still water significantly prolonged gastric residence compared to non-effervescent granules with still water, indicating that mixing of drugs into chyme was not motility-mediated.
Article
Pharmacology & Pharmacy
Tobias Auel, Lara Paula Scherke, Stefan Hadlich, Susan Mouchantat, Michael Grimm, Werner Weitschies, Anne Seidlitz
Summary: The behavior of intravitreal dosage forms in vivo is usually studied through animal experiments during preclinical development. However, the use of in vitro vitreous substitutes (VS) for preclinical investigations has not been sufficiently explored. This study compared the distribution of a contrast agent in hyaluronic acid agar gels and polyacrylamide gels with that in ex vivo porcine vitreous using magnetic resonance imaging. The results showed that while both gels could not completely represent the porcine vitreous body, the distribution in the polyacrylamide gel was similar. On the other hand, the distribution in the hyaluronic acid agar gel was much faster. Anatomical features such as the lens and interfacial tension could also affect the distribution, making it difficult to reproduce using in vitro VS.
Review
Pharmacology & Pharmacy
Henriette Hummler, Dorota Sarwinska, Werner Weitschies, Maik Gollasch, Susanne Page
Summary: This review article provides a brief overview of medication management, including aspects such as stock maintenance, understanding instructions, coping with packaging, and preparation prior to use. The main focus is on drug intake and the current understanding of dosing conditions in older adults and geriatric patients. With a better understanding of their needs and acceptability of different dosage forms, more patient-centric drug products can be designed.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Polymer Science
Friederike Brokmann, Franziska Feindt, Werner Weitschies, Christoph Rosenbaum
Summary: This study developed two test setups for an esophageal peristalsis model to simulate the behavior of dosage forms in the esophagus. The stimulated mode resulted in shorter clearance time of the dosage form compared to the unstimulated mode. Esophageal-applied films had a prolonged transit time compared to a viscous syrup. The modified simulated esophageal surface helped estimate the retention time of the dosage forms, which depended on various interacting parameters.
Review
Pharmacology & Pharmacy
Mirko Koziolek, Patrick Augustijns, Constantin Berger, Rodrigo Cristofoletti, David Dahlgren, Janneke Keemink, Paer Matsson, Fiona McCartney, Marco Metzger, Mario Mezler, Janis Niessen, James E. Polli, Maria Vertzoni, Werner Weitschies, Jennifer Dressman
Summary: This review discusses various methodologies used to determine drug permeability in the human gastrointestinal tract, including in vitro, in silico, and in vivo approaches. It highlights advancements in novel techniques such as computational approaches and gut-on-chip models. The review also explores the impact of permeability estimations on PK predictions and the importance of drug permeability in clinical studies.
Article
Pharmacology & Pharmacy
Theodora Tzakri, Lara Rehenbrock, Stefan Senekowitsch, Adrian Rump, Philipp Schick, Julius Krause, Marie-Luise Kromrey, Michael Grimm, Werner Weitschies
Summary: A compression-coated tablet was developed as an alternative to the ice capsule for determining gastric emptying. It showed no significant differences compared to the ice capsule and can be used in special populations.
Article
Chemistry, Medicinal
Dariah-Sohreh Seradj, Regine Beeck, Annika Haase, Julius Krause, Philipp Schick, Werner Weitschies
Summary: The microbiome of the colon is highly diverse and is influenced by various factors such as diet and lifestyle. This study aimed to investigate the impact of different microbiota on the degradation of sulfasalazine, a drug. The in vitro model MimiCol(3) was used to simulate the physiological conditions of the ascending colon. Stool samples from individuals with different diets were cultured, and although the bacterial composition was aligned by the nutrient medium used, similar degradation of sulfasalazine was observed in all microbiota studied in MimiCol(3), indicating the suitability of this model for gut microbiome metabolism studies.
