SHORT COMMUNICATION
 
KEYWORDS
TOPICS
ABSTRACT
Many artificial systems simulate the physiological state of the human gastrointestinal tract (GIT) and its separate compartments. These systems have the biorelevant media and imitate the physical forces and transit times of the GIT compartments, however, they lack the food-related and withincompartmental regulations and thus issues with translation of the data obtained to clinics arise. We aimed to introduce an alternative, simple and reliable ex vivo system which can be used in a laboratory setting, using fresh chyme from fed or fasted animals (pigs) to study the release profile of various drugs. For the present study we used porcine chyme collected from different gut compartments (stomach, duodenum and ileum) of six cross-bred male pigs in the fed state. Five different formulations of urate oxidase from Candida utilis were used as examples of tested drug substances. The performance of each formulation was tested by incubation in chyme at 37 °C for up to 4 h in the presence of uric acid. Samples were taken during the whole incubation time and the uric acid levels were estimated. The proposed ex vivo system provides information about the stability and performance of active drug substances in different gut compartments and can be used to test different formulations, assess possible drug-drug interactions, and the effects of fed and fasted conditions on the test substance of interest in the small and large intestine, taking into consideration diet-related changes in GIT secretions and intercompartmental regulation.
CONFLICT OF INTEREST
The Authors declare that there is no conflict of interest.
 
REFERENCES (27)
1.
Bellmann S., Lelieveld J., Gorissen T., Minekus M., Havenaar R., 2016. Development of an advanced in vitro model of the stomach and its evaluation versus human gastric physiology. Food Res. Int. 88, 191–198, https://doi.org/10.1016/j.food....
 
2.
Bergen W.G., 2022. Pigs (Sus Scrofa) in Biomedical Research. In: G. Wu (Editor). Recent Advances in Animal Nutrition and Metabolism. Advances in Experimental Medicine and Biology, vol. 1354. Cham (CH): Springer, https://doi.org/10.1007/978-3-....
 
3.
Díaz L., Zambrano E., Flores M.E. et al., 2020. Ethical considerations in animal research: The principle of 3R's. Rev. Invest. Clin. 73(4), 199–209, https://doi.org/10.24875/RIC.2....
 
4.
de La Pomelie D., Santé-Lhoutellier V., Sayd T., Theron L., Gatellier Ph., 2019. Using a dynamic artificial digestive system to investigate heme iron nitrosylation during gastro-intestinal transit. Food Chem. 281, 231–235, https://doi.org/10.1016/j.food....
 
5.
Cuche G., Malbert C-H., 1998. Relationships between cecoileal reflux and ileal motor patterns in conscious pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 274, G35–G41, https://doi.org/10.1152/ajpgi.....
 
6.
Guerra A., Denis S., le Goff O. et al., 2016. Development and validation of a new dynamic computer-controlled model of the human stomach and small intestine. Biotechnol. Bioeng. 113, 1325–1335, https://doi.org/10.1002/bit.25....
 
7.
Hăbeanu M., Lefter N.A., Toma S.M., Dumitru M., Cismileanu A., Surdu I., Gheorghe A., Dragomir C., Untea A., 2022. Changes in ileum and cecum volatile fatty acids and their relationship with microflora and enteric methane in pigs fed different fiber levels. Agriculture 12, 451, https://doi.org/10.3390/agricu....
 
8.
Henze L.J., Koehl N.J., Bennett-Lenane H., Holm R., Grimm M., Schneider F., Weitschies W., Koziolek M., Griffin B.T., 2021. Characterization of gastrointestinal transit and luminal conditions in pigs using a telemetric motility capsule. Eur. J. Pharm. Sci. 156, 105627, https://doi.org/10.1016/j.ejps....
 
9.
Kong F., Singh R.P., 2010. A human gastric simulator (HGS) to study food digestion in human stomach. J. Food Sci. 75, E627–E635, https://doi.org/10.1111/j.1750....
 
10.
Lex T.R., Rodriguez J.D., Zhang L., Jiang W., Gao Z., 2022. Development of in vitro dissolution testing methods to simulate fed conditions for immediate release solid oral dosage forms. AAPS J. 24,40, https://doi.org/10.1208/s12248....
 
11.
Li M., Zhao P., Pan Y., Wagner C., 2018. Predictive performance of physiologically based pharmacokinetic models for the effect of food on oral drug absorption: current status. CPT Pharmacometrics Syst. Pharmacol. 7, 82–89, https://doi.org/10.1002/psp4.1....
 
12.
Liu W., Ye A., Han F., Han J., 2019. Advances and challenges in liposome digestion: surface interaction, biological fate, and GIT modeling. Adv. Colloid. Interface Sci. 263, 52–67, https://doi.org/10.1016/j.cis.....
 
13.
Louyot P., Montet Y., Roland J., Pourel J., 1970. L'urate-oxydase dans le traitement de la goutte et de l'hyperuricémie [Urate ox-idase in the treatment of gout and hyperuricemia]. Rev. Rhum. Mal. Osteoartic. 37, 795–808.
 
14.
Miralles B., del Barrio R., Cueva C., Recio I., Amigo L., 2018. Dynamic gastric digestion of a commercial whey protein concentrate. J. Sci. Food Agric. 98, 1873–1879, https://doi.org/10.1002/jsfa.8....
 
15.
Pierzynowska K., Deshpande A., Mosiichuk N., et al., 2020. Oral treatment with an engineered uricase, ALLN-346, reduces hyperuricemia, and uricosuria in urate oxidase-deficient mice. Front. Med. 7, 569215, https://doi.org/10.3389/fmed.2....
 
16.
Roura E., Koopmans S.J., Lallès J.P., Le Huerou-Luron I., de Jager N., Schuurman T., Val-Laillet D., 2016. Critical review evaluating the pig as a model for human nutritional physiology. Nutr. Res. Rev. 29, 60–90, https://doi.org/10.1017/S09544....
 
17.
Sager J.E., Yu J., Ragueneau-Majlessi I., Isoherranen N., 2015. Physiologically based pharmacokinetic (PBPK) modeling and simulation approaches: a systematic review of published models, applications, and model verification. Drug Metab. Dispos. 43, 1823–1837, DOI: 10.1124/dmd.115.065920.
 
18.
Sensoy I., 2021. A review on the food digestion in the digestive tract and the used in vitro models. Curr. Res. Food. Sci. 4, 308–319, https://doi.org/10.1016/j.crfs....
 
19.
Sherman M.R., Saifer M.G., Perez-Ruiz F., 2008. PEG-uricase in the management of treatment-resistant gout and hyperuricemia. Adv. Drug. Deliv. Rev. 60, 59–68, https://doi.org/10.1016/j.addr....
 
20.
Staniszewska M., Romański M., Polak S., et al., 2023. A rational approach to predicting immediate release formulation behavior in multiple gastric motility patterns: a combination of a biorelevant apparatus, design of experiments, and machine learning. Pharmaceutics 15, 2056, https://doi.org/10.3390/pharma....
 
21.
Szczurek P., Mosiichuk N., Woliński J., et al., 2017. Oral uricase eliminates blood uric acid in the hyperuricemic pig model. PLOS One. 12, e0179195, https://doi.org/10.1371/journa....
 
22.
Tajima K., Aminov R., 2015. Structure and function of a nonruminant gut: a porcine model. In: A. Puniya, R. Singh, Kamra, D. (Editors) Rumen Microbiology: From Evolution to Revolution. Springer, New Delhi, https://doi.org/10.1007/978-81....
 
23.
Tistaert C., Heimbach T., Xia B., Parrott N., Samant T.S., Kesisoglou F., 2019. Food effect projections via physiologically based pharmacokinetic modeling: predictive case studies. J. Pharm. Sci. 108, 592–602, https://doi.org/10.1016/j.xphs....
 
24.
Verhoeckx K., Cotter P., López-Expósito I., Kleiveland C., Lea T., Mackie A., Requena T., Swiatecka D., Wichers H. (Editors), 2015. COST Action FA1005 The Impact of Food Bio-Actives on Gut Health: In Vitro and Ex Vivo Models. Cham (CH): Springer, https://doi.org/10.1007/978-3-....
 
25.
Wang J., Wu P., Liu M., Liao Z., Wang Y., Dong Z., Chen X.D., 2019. An advanced near real dynamic: in vitro human stomach system to study gastric digestion and emptying of beef stew and cooked rice. Food Funct. 10, 2914–2925, https://doi.org/10.1039/c8fo02....
 
26.
Wickham M.J.S., Faulks R.M., Mann J., Mandalari G., 2012. The design, operation, and application of a dynamic gastric model. Dissolution Technol. 19, 15–22, https://doi.org/10.14227/DT190....
 
27.
Yip K., Braverman G., Yue L., Fields T., 2023. Pipeline therapies for gout. Curr. Rheumatol. Rep. 26, 69–80, https://doi.org/10.1007/s11926....
 
ISSN:1230-1388
Journals System - logo
Scroll to top