Effects of Drugs and Excipients on Hydration Status

Ana M Puga, Sara Lopez-Oliva, Carmen Trives, Teresa Partearroyo, Gregorio Varela-Moreiras, Ana M Puga, Sara Lopez-Oliva, Carmen Trives, Teresa Partearroyo, Gregorio Varela-Moreiras

Abstract

Despite being the most essential nutrient, water is commonly forgotten in the fields of pharmacy and nutrition. Hydration status is determined by water balance (the difference between water input and output). Hypohydration or negative water balance is affected by numerous factors, either internal (i.e., a lack of thirst sensation) or external (e.g., polypharmacy or chronic consumption of certain drugs). However, to date, research on the interaction between hydration status and drugs/excipients has been scarce. Drugs may trigger the appearance of hypohydration by means of the increase of water elimination through either diarrhea, urine or sweat; a decrease in thirst sensation or appetite; or the alteration of central thermoregulation. On the other hand, pharmaceutical excipients induce alterations in hydration status by decreasing the gastrointestinal transit time or increasing the gastrointestinal tract rate or intestinal permeability. In the present review, we evaluate studies that focus on the effects of drugs/excipients on hydration status. These studies support the aim of monitoring the hydration status in patients, mainly in those population segments with a higher risk, to avoid complications and associated pathologies, which are key axes in both pharmaceutical care and the field of nutrition.

Keywords: adverse effects; chronic treatment; dehydration; drug interactions; elderly; excipients; hydration status; pharmaceutical care; polypharmacy; water balance.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Hooper L., Bunn D., Jimoh F.O., Fairweather-Tait S.J. Water-loss dehydration and aging. Mech. Ageing Dev. 2014;136–137 doi: 10.1016/j.mad.2013.11.009.
    1. Serra Majem L., Gil A. Conclusions of the I International and III National Hydration Congress Madrid, Spain 3rd and 4th December. Rev. Esp. Nutr. Comunit. 2014;20:2–12.
    1. Aranceta-Bartrina J., Gil Á., Marcos A., Pérez-Rodrigo C., Serra-Majem L., Varela-Moreiras G., Drewnowski A., Palou A., Anadón A., Murray B., et al. Conclusions of the II International and IV Spanish Hydration Congress. Toledo, Spain, 2nd-4th December, 2015. Nutr. Hosp. 2016;33:308. doi: 10.20960/nh.308.
    1. Armstrong L.E., Kenefick R.W., Castellani J.W., Riebe D., Kavouras S.A., Kuznicki J.T., Maresh C.M. Bioimpedance spectroscopy technique: Intra-, extracellular, and total body water. Med. Sci. Sports Exerc. 1997;29:1657–1663. doi: 10.1097/00005768-199712000-00017.
    1. World Health Organization . World Report of Ageing and Health. World Health Organization; Geneva, Switzerland: 2015.
    1. McKinley M.J., Johnson A.K. The physiological regulation of thirst and fluid intake. News Physiol. Sci. 2004;19:1–6. doi: 10.1152/nips.01470.2003.
    1. Schols J.M., De Groot C.P., van der Cammen T.J., Olde Rikkert M.G. Preventing and treating dehydration in the elderly during periods of illness and warm weather. J. Nutr. Health Aging. 2009;13:150–157. doi: 10.1007/s12603-009-0023-z.
    1. EFSA Panel on Dietetic Products, Nutrition, and Allergies Scientific Opinion on Dietary reference values for water. EFSA J. 2010;8:1459.
    1. Gandy J. Water intake: Validity of population assessment and recommendations. Eur. J. Nutr. 2015;54:11–16. doi: 10.1007/s00394-015-0944-8.
    1. Shires T.G., Shires Ill T.G., Lowry S.R. In: Principles of Surgery. 6th ed. Schwartz S.E., editor. Mc Graw-Hill; New York, NY, USA: 1994. pp. 61–80.
    1. Iglesias Rosado C., Villarino Marín A.L., Martínez J.A., Cabrerizo L., Gargallo M., Lorenzo H., Quiles J., Planas M., Polanco I., Romero de Ávila D., et al. Importance of water in the hydration of the Spanish population: FESNAD 2010 document. Nutr. Hosp. 2011;26:27–36.
    1. Begg D.P. Disturbances of thirst and fluid balance associated with aging. Physiol. Behav. 2017;178:28–34. doi: 10.1016/j.physbeh.2017.03.003.
    1. Dmitrieva N.I., Burg M.B. Increased insensible water loss contributes to aging related dehydration. PLoS ONE. 2011;6 doi: 10.1371/journal.pone.0020691.
    1. Perrier E., Rondeau P., Poupin M., Le Bellego L., Armstrong L.E., Lang F., Stookey J., Tack I., Vergne S., Klein A. Relation between urinary hydration biomarkers and total fluid intake in healthy adults. Eur. J. Clin. Nutr. 2013;67:939–943. doi: 10.1038/ejcn.2013.93.
    1. Perrier E., Vergne S., Klein A., Poupin M., Rondeau P., Le Bellego L., Armstrong L.E., Lang F., Stookey J., Tack I. Hydration biomarkers in free-living adults with different levels of habitual fluid consumption. Br. J. Nutr. 2013;109:1678–1687. doi: 10.1017/S0007114512003601.
    1. Armstrong L.E. Assessing hydration status: The elusive gold standard. J. Am. Coll. Nutr. 2007;26:575S–584S. doi: 10.1080/07315724.2007.10719661.
    1. Shirreffs S.M. Markers of hydration status. Eur. J. Clin. Nutr. 2003;57:S6–S9. doi: 10.1038/sj.ejcn.1601895.
    1. Gandy J., Martinez H., Guelinckx I., Moreno L.A., Bardosono S., Salas-Salvadó J., Kavouras S.A. Relevance of Assessment Methods for Fluid Intake. Ann. Nutr. Metab. 2016;68:1–5. doi: 10.1159/000446197.
    1. Popkin B.M., D’Anci K.E., Rosenberg I.H. Water, hydration, and health. Nutr. Rev. 2010;68:439–458. doi: 10.1111/j.1753-4887.2010.00304.x.
    1. Clarke T.A., Markarian M., Griswold W., Mendoza S. Hypernatremic dehydration resulting from inadequate breast-feeding. Pediatrics. 1979;63:931–932.
    1. D’Anci K.E., Rosenberg I.H., Constant F. Hydration and Cognitive Function in Children. Nutr. Rev. 2006;64:457–464. doi: 10.1111/j.1753-4887.2006.tb00176.x.
    1. Jéquier E., Constant F. Water as an essential nutrient: The physiological basis of hydration. Eur. J. Clin. Nutr. 2010;64:115–123. doi: 10.1038/ejcn.2009.111.
    1. Ferry M. Strategies for ensuring good hydration in the elderly. Nutr. Rev. 2005;63:S22–S29. doi: 10.1111/j.1753-4887.2005.tb00151.x.
    1. Denaro C.P., Brown C.R., Jacob P., III, Benowitz N.L. Effects of caffeine with repeated dosing. Eur. J. Clin. Pharmacol. 1991;40:273–278. doi: 10.1007/BF00315208.
    1. Bartoli E., Castello L., Fumo E., Pirisi M. Electrolyte derangements and diuretic misuse in the elderly. Arch. Gerontol. Geriatr. 2002;8:43–52. doi: 10.1016/S0167-4943(02)00103-6.
    1. Westaway K., Frank O., Husband A., McClure A., Shute R., Edwards S., Curtis J., Rowett D. Medicines can affect thermoregulation and accentuate the risk of dehydration and heat-related illness during hot weather. J. Clin. Pharm. Ther. 2015;40:363–367. doi: 10.1111/jcpt.12294.
    1. Benelam B., Wyness L. Hydration and health: A review. Nutr. Bull. 2010;35:3–25. doi: 10.1111/j.1467-3010.2009.01795.x.
    1. Polhuis K.C.M.M., Wijnen A.H.C., Sierksma A., Calame W., Tieland M. The Diuretic Action of Weak and Strong Alcoholic Beverages in Elderly Men: A Randomized Diet-Controlled Crossover Trial. Nutrients. 2017;9:E660. doi: 10.3390/nu9070660.
    1. Hajat S., O’Connor M., Kosatsky T. Health effects of hot weather: From awareness of risk factors to effective health protection. Lancet. 2010;375:856–863. doi: 10.1016/S0140-6736(09)61711-6.
    1. Davidhizar R., Dunn C.L., Hart A.N. A review of the literature on how important water is to the world’s elderly population. Int. Nurs. Rev. 2004;51:159–166. doi: 10.1111/j.1466-7657.2004.00224.x.
    1. Kalisch Ellett L.M., Pratt N.L., Le Blanc V.T., Westaway K., Roughead E.E. Increased risk of hospital admission for dehydration or heat-related illness after initiation of medicines: A sequence symmetry analysis. J. Clin. Pharm. Ther. 2016;41:503–507. doi: 10.1111/jcpt.12418.
    1. Rowett D. Medicines and heatwaves. RGH Pharmacy e-Bulletin. 2013;49:1.
    1. Chassany O., Michaux A., Bergmann J.F. Drug-induced diarrhoea. Drug Saf. 2000;22:53–72. doi: 10.2165/00002018-200022010-00005.
    1. Abraham B.P., Sellin J.H. Drug-induced, factitious, & idiopathic diarrhoea. Best Pract. Res. Clin. Gastroenterol. 2012;26:633–648.
    1. Ratnaike R.N., Jones T.E. Mechanisms of drug-induced diarrhoea in the elderly. Drugs Aging. 1998;13:245–253. doi: 10.2165/00002512-199813030-00007.
    1. Puga A.M., Partearroyo T., Varela-Moreiras G. Hydration status, drug interactions, and determinants in a Spanish elderly population: A pilot study. J. Physiol. Biochem. 2018;74:139–151. doi: 10.1007/s13105-017-0585-x.
    1. Ashford M. La Ciencia Del Diseño De Las Formas Farmacéuticas. Elsevier; Madrid, Spain: 2004. Biodisponibilidad: Factores fisicoquímicos y de la forma farmacéutica.
    1. WHO Collaborating Centre for Drug Statistics Methodology Structure and Principles. [(accessed on 4 September 2018)]; Available online:
    1. Bouchoucha M., Uzzan B., Cohen R. Metformin and digestive disorders. Diabetes Metab. 2011;37:90–96. doi: 10.1016/j.diabet.2010.11.002.
    1. Chaudhury A., Duvoor C., Dendi V.S.R., Kraleti S., Chada A., Ravilla R., Marco A., Shekhawat N.S., Montales M.T., Kuriakose K., et al. Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management. Front Endocrinol. 2017;8 doi: 10.3389/fendo.2017.00006.
    1. Cubeddu L.X., Bönisch H., Göthert M., Molderings G., Racké K., Ramadori G., Miller K.J., Schwörer H. Effects of metformin on intestinal 5-hydroxytryptamine (5-HT) release and on 5-HT3 receptors. Naunyn Schmiedebergs Arch. Pharmacol. 2000;361:85–91. doi: 10.1007/s002109900152.
    1. McCreight L.J., Bailey C.J., Pearson E.R. Metformin and the gastrointestinal tract. Diabetologia. 2016;59:426–435. doi: 10.1007/s00125-015-3844-9.
    1. Scarpello J.H., Hodgson E., Howlett H.C. Effect of metformin on bile salt circulation and intestinal motility in type 2 diabetes mellitus. Diabet. Med. 1998;15:651–656. doi: 10.1002/(SICI)1096-9136(199808)15:8<651::AID-DIA628>;2-A.
    1. Field M. Intestinal ion transport and the pathophysiology of diarrhea. J. Clin. Investig. 2003;111:931–943. doi: 10.1172/JCI200318326.
    1. Silverstein F.E., Graham D.Y., Senior J.R., Davies H.W., Struthers B.J., Bittman R.M., Geis G.S. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 1995;123:241–249. doi: 10.7326/0003-4819-123-4-199508150-00001.
    1. Herting R.L., Clay G.A. Overview of clinical safety with misoprostol. Dig. Dis. Sci. 1985;30:185S–193S. doi: 10.1007/BF01309407.
    1. Graham D.Y., White R.H., Moreland L.W., Schubert T.T., Katz R., Jaszewski R., Tindall E., Triadafilopoulos G., Stromatt S.C., Teoh L.S. Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group. Ann. Intern. Med. 1993;119:257–262. doi: 10.7326/0003-4819-119-4-199308150-00001.
    1. Lopez Morra H.A., Fine S.N., Dickstein G. Colonic ischemia with laxative use in young adults. Am. J. Gastroenterol. 2005;100:2134–2136. doi: 10.1111/j.1572-0241.2005.50395_8.x.
    1. Parízek A., Simják P., Cerný A., Sestinová A., Zdenková A., Hill M., Dusková M., Vlk R., Kokrdová Z., Koucký M., et al. Efficacy and safety of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy. Ann. Hepatol. 2016;15:757–761.
    1. Keszthelyi D., Jansen S.V., Schouten G.A., de Kort S., Scholtes B., Engels L.G., Masclee A.A. Proton pump inhibitor use is associated with an increased risk for microscopic colitis: A case-control study. Aliment. Pharmacol. Ther. 2010;32:1124–1128. doi: 10.1111/j.1365-2036.2010.04453.x.
    1. Beaugerie L., Pardi D.S. Review article: Drug-induced microscopic colitis - proposal for a scoring system and review of the literature. Aliment. Pharmacol. Ther. 2005;22:277–284. doi: 10.1111/j.1365-2036.2005.02561.x.
    1. Wilcox G.M., Mattia A.R. Microscopic colitis associated with omeprazole and esomeprazole exposure. J. Clin. Gastroenterol. 2009;43:551–553. doi: 10.1097/MCG.0b013e31817d3fa1.
    1. Verhaegh B.P., de Vries F., Masclee A.A., Keshavarzian A., de Boer A., Souverein P.C., Pierik M.J., Jonkers D.M. High risk of drug-induced microscopic colitis with concomitant use of NSAIDs and proton pump inhibitors. Aliment. Pharmacol. Ther. 2016;43:1004–1013. doi: 10.1111/apt.13583.
    1. Masclee G.M., Coloma P.M., Kuipers E.J., Sturkenboom M.C. Increased risk of microscopic colitis with use of proton pump inhibitors and non-steroidal anti-inflammatory drugs. Am. J. Gastroenterol. 2015;110:749–759. doi: 10.1038/ajg.2015.119.
    1. Singh A., Cresci G.A., Kirby D.F. Proton Pump Inhibitors: Risks and Rewards and Emerging Consequences to the Gut Microbiome. Nutr. Clin. Pract. 2018;33:614–624. doi: 10.1002/ncp.10181.
    1. Imhann F., Bonder M.J., Vich Vila A., Fu J., Mujagic Z., Vork L., Tigchelaar E.F., Jankipersadsing S.A., Cenit M.C., Harmsen H.J., et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65:740–748. doi: 10.1136/gutjnl-2015-310376.
    1. Kles K.A., Vavricka S.R., Turner J.R., Musch M.W., Hanauer S.B., Chang E.B. Comparative analysis of the in vitro prosecretory effects of balsalazide, sulfasalazine, olsalazine, and mesalamine in rabbit distal ileum. Inflamm. Bowel. Dis. 2005;11:253–257. doi: 10.1097/01.MIB.0000160806.53858.55.
    1. Vanderperren B., Rizzo M., Angenot L., Haufroid V., Jadoul M., Hantson P. Acute liver failure with renal impairment related to the abuse of senna anthraquinone glycosides. Ann. Pharmacother. 2005;39:1353–1357. doi: 10.1345/aph.1E670.
    1. Farraye F.A., Peppercorn M.A., Steer M.L., Joffe N., Rees M. Acute small-bowel mucosal edema following enalapril use. JAMA. 1988;259:3131. doi: 10.1001/jama.1988.03720210021021.
    1. Marietta E.V., Cartee A., Rishi A., Murray J.A. Drug-induced enteropathy. Dig. Dis. 2015;33:215–220. doi: 10.1159/000370205.
    1. Tran T.H., Li H. Olmesartan and drug-induced enteropathy. Pharm. Ther. 2014;39:47–50.
    1. Rubio-Tapia A., Herman M.L., Ludvigsson J.F., Kelly D.G., Mangan T.F., Wu T.T., Murray J.A. Severe Spruelike Enteropathy Associated With Olmesartan. Mayo. Clin. Proc. 2012;87:732–738. doi: 10.1016/j.mayocp.2012.06.003.
    1. Marthey L., Cadiot G., Seksik P., Pouderoux P., Lacroute J., Skinazi F., Mesnard B., Chayvialle J.A., Savoye G., Druez A., et al. Olmesartan-associated enteropathy: Results of a national survey. Aliment. Pharmacol. Ther. 2014;40:1103–1109. doi: 10.1111/apt.12937.
    1. Padwal R., Lin M., Etminan M., Eurich D.T. Comparative effectiveness of olmesartan and other angiotensin receptor blockers in diabetes mellitus: Retrospective cohort study. Hypertension. 2014;63:977–983. doi: 10.1161/HYPERTENSIONAHA.113.02855.
    1. Herman M.L., Rubio-Tapia A., Wu T.T., Murray J.A. A Case of Severe Sprue-Like Enteropathy Associated With Valsartan. ACG Case. Rep. J. 2015;2:92–94. doi: 10.14309/crj.2015.15.
    1. Smith H., Battjes E., Yan S., Kaakeh Y. Chronic Digoxin Toxicity Precipitated by Dronedarone. Ann. Pharmacother. 2014;48:923–927. doi: 10.1177/1060028014530106.
    1. Pincus M. Management of digoxin toxicity. Aust. Prescr. 2016;39:18–20. doi: 10.18773/austprescr.2016.006.
    1. Vodusek Z., Feuerstadt P., Brandt L.J. Review article: The pharmacological causes of colon ischaemia. Aliment. Pharmacol. Ther. 2019;49:51–63. doi: 10.1111/apt.15052.
    1. Nozawa H., Akiyama Y., Sunaga S., Tsurita G. Ischemic colitis following colonoscopy in an elderly patient on cardiovascular medication. Endoscopy. 2007;39:E344–E345. doi: 10.1055/s-2007-995329.
    1. Pentland B., Pennington C.R. Acute diarrhoea in the elderly. Age Ageing. 1980;9:90–92. doi: 10.1093/ageing/9.2.90.
    1. Stöllberger C., Lutz W., Finsterer J. Heat-related side-effects of neurological and non-neurological medication may increase heatwave fatalities. Eur. J. Neurol. 2009;16:879–882. doi: 10.1111/j.1468-1331.2009.02581.x.
    1. Bonderup O.K., Fenger-Grøn M., Wigh T., Pedersen L., Nielsen G.L. Drug exposure and risk of microscopic colitis: A nationwide Danish case-control study with 5751 cases. Inflamm. Bowel. Dis. 2014;20:1702–1707. doi: 10.1097/MIB.0000000000000143.
    1. Fernández-Bañares F., Esteve M., Espinós J.C., Rosinach M., Forné M., Salas A., Viver J.M. Drug consumption and the risk of microscopic colitis. Am. J. Gastroenterol. 2007;102:324–330. doi: 10.1111/j.1572-0241.2006.00902.x.
    1. Lucendo A.J. Drug Exposure and the Risk of Microscopic Colitis: A Critical Update. Drugs RD. 2017;17:79–89. doi: 10.1007/s40268-016-0171-7.
    1. Magaz Martínez M., Relea Pérez L., Suárez Ferrer C., Barrios Peinado C., Abreu García L. Silodosin: An overlooked cause of drug-induced diarrhea. Gastroenterol. Hepatol. 2016;39:526–527. doi: 10.1016/j.gastrohep.2015.07.008.
    1. Marks L.S., Gittelman M.C., Hill L.A., Volinn W., Hoel G. Silodosin in the treatment of the signs and symptoms of benign prostatic hyperplasia: A 9-month, open-label extension study. Urology. 2009;74:1318–1322. doi: 10.1016/j.urology.2009.06.072.
    1. Bartlett J.G. Clinical practice. Antibiotic-associated diarrhea. N. Engl. J. Med. 2002;346:334–339. doi: 10.1056/NEJMcp011603.
    1. Croom K.F., Goa K.L. Levofloxacin: A review of its use in the treatment of bacterial infections in the United States. Drugs. 2003;63:2769–2802. doi: 10.2165/00003495-200363240-00008.
    1. Dobbins W.O., III, Herrero B.A., Mansbach C.M. Morphologic alterations associated with neomycin induced malabsorption. Am. J. Med. Sci. 1968;255:63–77. doi: 10.1097/00000441-196801000-00011.
    1. Easton J., Noble S., Perry C.M. Amoxicillin/clavulanic acid: A review of its use in the management of paediatric patients with acute otitis media. Drugs. 2003;63:311–340. doi: 10.2165/00003495-200363030-00005.
    1. Gillies M., Ranakusuma A., Hoffmann T., Thorning S., McGuire T., Glasziou P., Del Mar C. Common harms from amoxicillin: A systematic review and meta-analysis of randomized placebo-controlled trials for any indication. CMAJ. 2015;187:E21–E31. doi: 10.1503/cmaj.140848.
    1. Hansen M.P., Scott A.M., McCullough A., Thorning S., Aronson J.K., Beller E.M., Glasziou P.P., Hoffmann T.C., Clark J., Del Mar C.B. Adverse events in people taking macrolide antibiotics versus placebo for any indication. Cochrane. Database. Syst. Rev. 2019;1:CD011825. doi: 10.1002/14651858.CD011825.pub2.
    1. Łukasik J., Szajewska H. Effect of a multispecies probiotic on reducing the incidence of antibiotic-associated diarrhoea in children: A protocol for a randomised controlled trial. BMJ Open. 2018;8 doi: 10.1136/bmjopen-2017-021214.
    1. Turck D., Bernet J.P., Marx J., Kempf H., Giard P., Walbaum O., Lacombe A., Rembert F., Toursel F., Bernasconi P., et al. Incidence and risk factors of oral antibiotic-associated diarrhea in an outpatient pediatric population. J. Pediatr. Gastroenterol. Nutr. 2003;37:22–26. doi: 10.1097/00005176-200307000-00004.
    1. Arslan H., Inci E.K., Azap O.K., Karakayali H., Torgay A., Haberal M. Etiologic agents of diarrhea in solid organ recipients. Transpl. Infect. Dis. 2007;9:270–275. doi: 10.1111/j.1399-3062.2007.00237.x.
    1. Kamar N., Faure P., Dupuis E., Cointault O., Joseph-Hein K., Durand D., Moreau J., Rostaing L. Villous atrophy induced by mycophenolate mofetil in renal-transplant patients. Transpl. Int. 2004;17:463–467. doi: 10.1111/j.1432-2277.2004.tb00471.x.
    1. Papadimitriou J.C., Cangro C.B., Lustberg A., Khaled A., Nogueira J., Wiland A., Ramos E., Klassen D.K., Drachenberg C.B. Histologic features of mycophenolate mofetil-related colitis: A graft-versus-host disease-like pattern. Int. J. Surg. Pathol. 2003;11:295–302. doi: 10.1177/106689690301100406.
    1. Ziegler T.R., Fernández-Estívariz C., Gu L.H., Fried M.W., Leader L.M. Severe villus atrophy and chronic malabsorption induced by azathioprine. Gastroenterology. 2003;124:1950–1957. doi: 10.1016/S0016-5085(03)00405-0.
    1. Iacovelli R., Pietrantonio F., Palazzo A., Maggi C., Ricchini F., de Braud F., Di Bartolomeo M. Incidence and relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5- fluorouracil: A meta-analysis of published trials. Br. J. Clin. Pharmacol. 2014;78:1228–1237. doi: 10.1111/bcp.12449.
    1. Loganayagam A., Arenas Hernandez M., Corrigan A., Fairbanks L., Lewis C.M., Harper P., Maisey N., Ross P., Sanderson J.D., Marinaki A.M. Pharmacogenetic variants in the DPYD, TYMS, CDA and MTHFR genes are clinically significant predictors of fluoropyrimidine toxicity. Br. J. Cancer. 2013;108:2505–2515. doi: 10.1038/bjc.2013.262.
    1. Schwab M., Zanger U.M., Marx C., Schaeffeler E., Klein K., Dippon J., Kerb R., Blievernicht J., Fischer J., Hofmann U., et al. Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: A prospective clinical trial by the German 5-FU Toxicity Study Group. J. Clin. Oncol. 2008;26:2131–2138. doi: 10.1200/JCO.2006.10.4182.
    1. Gibson R.J., Bowen J.M., Inglis M.R., Cummins A.G., Keefe D.M. Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer. J. Gastroenterol. Hepatol. 2003;18:1095–1100. doi: 10.1046/j.1440-1746.2003.03136.x.
    1. Sandmeier D., Chaubert P., Bouzourene H. Irinotecan-induced colitis. Int. J. Surg. Pathol. 2005;13:215–218. doi: 10.1177/106689690501300215.
    1. Kahl B.S., Spurgeon S.E., Furman R.R., Flinn I.W., Coutre S.E., Brown J.R., Benson D.M., Byrd J.C., Peterman S., Cho Y., et al. A phase 1 study of the PI3Kδ inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL) Blood. 2014;123:3398–3405. doi: 10.1182/blood-2013-11-537555.
    1. Burger J.A., Okkenhaug K. Haematological cancer: Idelalisib-targeting PI3Kδ in patients with B-cell malignancies. Nat. Rev. Clin. Oncol. 2014;11:184–186. doi: 10.1038/nrclinonc.2014.42.
    1. Coutré S.E., Barrientos J.C., Brown J.R., de Vos S., Furman R.R., Keating M.J., Li D., O’Brien S.M., Pagel J.M., Poleski M.H., et al. Management of adverse events associated with idelalisib treatment: Expert panel opinion. Leuk Lymphoma. 2015;56:2779–2786. doi: 10.3109/10428194.2015.1022770.
    1. Furman R.R., Sharman J.P., Coutre S.E., Cheson B.D., Pagel J.M., Hillmen P., Barrientos J.C., Zelenetz A.D., Kipps T.J., Flinn I., et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 2014;370:997–1007. doi: 10.1056/NEJMoa1315226.
    1. Suárez Del Olmo D., Corregidor Luna L., Hidalgo Correas F.J., García Benayas E., García Díaz B. Grave diarrhea associated with idelalisib administration. Farm Hosp. 2016;40:227–229.
    1. Kuo J.R., Davis A.D., Rodriguez E.A., Vela M.F., Heigh R.I., Salomao M.A., Gurudu S.R. Severe Diarrhea in the Setting of Immune Checkpoint Inhibitors. Case. Rep. Gastroenterol. 2018;12:704–708. doi: 10.1159/000493183.
    1. Graham D.Y., Opekun A.R., Willingham F.F., Qureshi W.A. Visible small-intestinal mucosal injury in chronic NSAID users. Clin. Gastroenterol. Hepatol. 2005;3:55–59. doi: 10.1016/S1542-3565(04)00603-2.
    1. Shin S.J., Noh C.K., Lim S.G., Lee K.M., Lee K.J. Non-steroidal anti-inflammatory drug-induced enteropathy. Intest. Res. 2017;15:446–455. doi: 10.5217/ir.2017.15.4.446.
    1. Ehrenfeld M., Levy M., Sharon P., Rachmilewitz D., Eliakim M. Gastrointestinal effects of long-term colchicine therapy in patients with recurrent polyserositis (familial mediterranean fever) Dig. Dis. Sci. 1982;27:723–727. doi: 10.1007/BF01393768.
    1. Stemmermann G.N., Hayashi T. Colchicine intoxication: A reappraisal of its pathology based on a study of three fatal cases. Hum. Pathol. 1971;2:321–332. doi: 10.1016/S0046-8177(71)80040-0.
    1. Verne G.N., Davis R.H., Robinson M.E., Gordon J.M., Eaker E.Y., Sninksy C.A. Treatment of chronic constipation with colchicine: Randomized, double-blind, placebo-controlled, crossover trial. Am. J. Gastroenterol. 2003;98:1112–1116.
    1. Verne G.N., Eaker E.Y., Davis R.H., Sninsky C.A. Colchicine is an effective treatment for patients with chronic constipation: An open-label trial. Dig. Dis. Sci. 1997;42:1959–1963. doi: 10.1023/A:1018883731556.
    1. Wallin B.A., McCafferty J.P., Fox M.J., Cooper D.R., Goldschmidt M.S. Incidence and management of diarrhea during long term auranofin therapy. J. Rheumatol. 1988;15:1755–1758.
    1. Magaró M., Altomonte L., Mirone L., Zoli A., Corvino G., Carelli G. Effect of oral gold salt therapy on bile acid absorption in rheumatoid arthritis patients. Clin. Rheumatol. 1990;9:42–47. doi: 10.1007/BF02030239.
    1. Larsen J.P., Worm-Petersen J., Sidén A., Gordin A., Reinikainen K., Leinonen M., NOMESAFE Study Group The tolerability and efficacy of entacapone over 3 years in patients with Parkinson’s disease. Eur. J. Neurol. 2003;10:137–146. doi: 10.1046/j.1468-1331.2003.00559.x.
    1. Rinne U.K., Larsen J.P., Siden A., Worm-Petersen J. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Nomecomt Study Group. Neurology. 1998;51:1309–1314. doi: 10.1212/WNL.51.5.1309.
    1. Cipriani A., Reid K., Young A.H., Macritchie K., Geddes J. Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder. Cochrane Database Syst. Rev. 2013;17:CD003196. doi: 10.1002/14651858.CD003196.pub2.
    1. Sellin J.H. The pathophysiology of diarrhea. Clin. Transplant. 2001;15:2–10. doi: 10.1111/j.1399-0012.2001.00002.x.
    1. Mordi N.A., Mordi I.R., Singh J.S., Baig F., Choy A.M., McCrimmon R.J., Struthers A.D., Lang C.C. Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): Protocol for a randomised controlled double-blind cross-over trial. BMJ Open. 2017;7 doi: 10.1136/bmjopen-2017-018097.
    1. Kimura G. Importance of inhibiting sodium-glucose cotransporter and its compelling indication in type 2 diabetes: Pathophysiological hypothesis. J. Am. Soc. Hypertens. 2016;10:271–278. doi: 10.1016/j.jash.2016.01.009.
    1. D’Elia J.A., Segal A.R., Weinrauch L.A. Metformin-SGLT2, Dehydration, and Acidosis Potential. J. Am. Geriatr. Soc. 2017;65:e101–e102. doi: 10.1111/jgs.14724.
    1. Khow K.S., Lau S.Y., Li J.Y., Yong T.Y. Diuretic-associated electrolyte disorders in the elderly: Risk factors, impact, management and prevention. Curr. Drug Saf. 2014;9:2–15. doi: 10.2174/1574886308666140109112730.
    1. Michenot F., Sommet A., Bagheri H., Lapeyre-Mestre M., Montastruc J.L. Adverse drug reactions in patients older than 70 years during the heat wave occurred in France in summer 2003: A study from the French PharmacoVigilance Database. Pharmacoepidemiol Drug Saf. 2006;15:735–740. doi: 10.1002/pds.1284.
    1. Faunt J.D., Wilkinson T.J., Aplin P., Henschke P., Webb M., Penhall R.K. The effete in the heat: Heat-related hospital presentations during a ten day heat wave. Aust. N. Z. J. Med. 1995;25:117–121. doi: 10.1111/j.1445-5994.1995.tb02822.x.
    1. Liamis G., Rodenburg E.M., Hofman A., Zietse R., Stricker B.H., Hoorn E.J. Electrolyte disorders in community subjects: Prevalence and risk factors. Am. J. Med. 2013;126:256–263. doi: 10.1016/j.amjmed.2012.06.037.
    1. Hunter R.W., Ivy J.R., Bailey M.A. Glucocorticoids and renal Na+ transport: Implications for hypertension and salt sensitivity. J. Physiol. 2014;592:1731–1744. doi: 10.1113/jphysiol.2013.267609.
    1. Berger S., Bleich M., Schmid W., Cole T.J., Peters J., Watanabe H., Kriz W., Warth R., Greger R., Schütz G. Mineralocorticoid receptor knockout mice: Pathophysiology of Na+ metabolism. Proc. Natl. Acad. Sci. USA. 1998;95:9424–9429. doi: 10.1073/pnas.95.16.9424.
    1. Liberopoulos E.N., Alexandridis G.H., Christidis D.S., Elisaf M.S. SIADH and hyponatremia with theophylline. Ann. Pharmacother. 2002;36:1180–1182. doi: 10.1345/aph.1A425.
    1. Sakai K., Agassandian K., Morimoto S., Sinnayah P., Cassell M.D., Davisson R.L., Sigmund C.D. Local production of angiotensin II in the subfornical organ causes elevated drinking. J. Clin. Investig. 2007;117:1088–1095. doi: 10.1172/JCI31242.
    1. Letmaier M., Painold A., Holl A.K., Vergin H., Engel R., Konstantinidis A., Kasper S., Grohmann R. Hyponatraemia during psychopharmacological treatment: Results of a drug surveillance programme. Int. J. Neuropsychopharmacol. 2012;15:739–748. doi: 10.1017/S1461145711001192.
    1. Mittleman G., Rosner A.L., Schaub C.L. Polydipsia and dopamine: Behavioral effects of dopamine D1 and D2 receptor agonists and antagonists. J. Pharmacol. Exp. Ther. 1994;271:638–650.
    1. Leth-Møller K.B., Hansen A.H., Torstensson M., Andersen S.E., Ødum L., Gislasson G., Torp-Pedersen C., Holm E.A. Antidepressants and the risk of hyponatremia: A Danish register-based population study. BMJ Open. 2016;6:e011200. doi: 10.1136/bmjopen-2016-011200.
    1. De Leon J., Verghese C., Stanilla J.K., Lawrence T., Simpson G.M. Treatment of polydipsia and hyponatremia in psychiatric patients. Can clozapine be a new option? Neuropsychopharmacology. 1995;12:133–138. doi: 10.1016/0893-133X(94)00069-C.
    1. Spears N.M., Leadbetter R.A., Shutty M.S., Jr. Clozapine treatment in polydipsia and intermittent hyponatremia. J. Clin. Psychiatry. 1996;57:123–128.
    1. Dreiher J., Porath A. Severe hyponatremia induced by theophylline and trimethoprim. Arch. Intern. Med. 2001;161:291–292. doi: 10.1001/archinte.161.2.291.
    1. Flack J.M., Ryder K.W., Strickland D., Whang R. Metabolic correlates of theophylline therapy: A concentration-related phenomenon. Ann. Pharmacother. 1994;28:175–179. doi: 10.1177/106002809402800202.
    1. Tudehope D., Burke J., Loadsman T. Syndrome of inappropriate antidiuretic hormone (SIADH) secretion in a preterm infant who was receiving oral theophylline. Aust. Paediatr. J. 1983;19:55.
    1. Tansey E.A., Johnson C.D. Recent advances in thermoregulation. Adv. Physiol. Educ. 2015;39:139–148. doi: 10.1152/advan.00126.2014.
    1. Freund B.J., Joyner M.J., Jilka S.M., Kalis J., Nittolo J.M., Taylor J.A., Peters H., Feese G., Wilmore J.H. Thermoregulation during prolonged exercise in heat: Alterations with beta-adrenergic blockade. J. Appl. Physiol. 1985;63:930–936. doi: 10.1152/jappl.1987.63.3.930.
    1. Martin-Latry K., Goumy M.P., Latry P., Gabinski C., Bégaud B., Faure I., Verdoux H. Psychotropic drugs use and risk of heat-related hospitalisation. Eur. Psychiatry. 2007;22:335–338. doi: 10.1016/j.eurpsy.2007.03.007.
    1. Mack G.W., Shannon L.M., Nadel E.R. Influence of beta-adrenergic blockade on the control of sweating in humans. J. Appl. Physiol. 1986;61:1701–1705. doi: 10.1152/jappl.1986.61.5.1701.
    1. Rivas E., McEntire S.J., Herndon D.N., Mlcak R.P., Suman O.E. β-Adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and nonburned skin under neutral and hot environments in children. Microcirculation. 2017;24 doi: 10.1111/micc.12350.
    1. Gudmundsdottir H., Aksnes H., Heldal K., Krogh A., Froyshov S., Rudberg N., Os I. Metformin and antihypertensive therapy with drugs blocking the renin angiotensin system, a cause of concern? Clin. Nephrol. 2006;66:380–385. doi: 10.5414/CNP66380.
    1. Stahlmann R., Lode H. Safety considerations of fluoroquinolones in the elderly: An update. Drugs Aging. 2010;27:193–209. doi: 10.2165/11531490-000000000-00000.
    1. Mason P. Important drug-nutrient interactions. Proc. Nutr. Soc. 2010;69:551–557. doi: 10.1017/S0029665110001576.
    1. Jałocha W., Walecka-Kapica E., Tomaszewska-Warda K., Chojnacki J., Klupińska G. The effect of fluoxetine and tianeptine on emotional and eating disorders in postmenopausal women. Pol. Merkur. Lekarski. 2014;37:35–38.
    1. Haas L. Management of diabetes mellitus medications in the nursing home. Drugs Aging. 2005;22:209–218. doi: 10.2165/00002512-200522030-00003.
    1. Munshi M.N., Florez H., Huang E.S., Kalyani R.R., Mupanomunda M., Pandya N., Swift C.S., Taveira T.H., WHaas L.B. Management of Diabetes in Long-term Care and Skilled Nursing Facilities: A Position Statement of the American Diabetes Association. Diabetes Care. 2016;39:308–318. doi: 10.2337/dc15-2512.
    1. FDA Revises Warnings Regarding Use of the Diabetes Medicine Metformin in Certain Patients with Reduced Kidney Function. [(accessed on 17 October 2018)]; Available online: .
    1. Wadworth A.N., Fitton A. Olsalazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in inflammatory bowel disease. Drugs. 1991;41:647–664. doi: 10.2165/00003495-199141040-00009.
    1. Ahn K. The worldwide trend of using botanical drugs and strategies for developing global drugs. BMB Rep. 2017;50:111–116. doi: 10.5483/BMBRep.2017.50.3.221.
    1. Di Lorenzo C., Ceschi A., Kupferschmidt H., Lüde S., De Souza Nascimento E., Dos Santos A., Colombo F., Frigerio G., Nørby K., Plumb J., et al. Adverse effects of plant food supplements and botanical preparations: A systematic review with critical evaluation of causality. Br. J. Clin. Pharmacol. 2015;79:578–592. doi: 10.1111/bcp.12519.
    1. Stickel F., Seitz H.K., Hahn E.G., Schuppan D. Liver toxicity of drugs of plant origin. Z. Gastroenterol. 2001;39:225–232. doi: 10.1055/s-2001-11772.
    1. Stöllberger C., Finsterer J. Did thirst-blockers like angiotensin-converting-enzyme inhibitors, sartans, serotonine-re-uptake-inhibitors, dopamine agonists/antagonists, or atypical neuroleptics contribute to the exorbitant number of fatalities during the French 2003 heat wave? Pharmacoepidemiol. Drug Saf. N. 2007;16:1252–1253. doi: 10.1002/pds.1456.
    1. Onteddu N.K., Pulivarthi V.S.K.K., Ginnavaram M., Kedika R. Olmesartan-induced enteropathy. BMJ Case Rep. 2018 doi: 10.1136/bcr-2018-224411.
    1. Summary of Product Characteristics Sylodix. [(accessed on 10 January 2019)]; Available online: .
    1. McFarland L.V. Antibiotic-associated diarrhea: Epidemiology, trends and treatment. Future Microbiol. 2008;3:563–578. doi: 10.2217/17460913.3.5.563.
    1. Nguyen N.Q., Yi Mei S.L. Current issues on safety of prokinetics in critically ill patients with feed intolerance. Ther. Adv. Drug Saf. 2011;2:197–204. doi: 10.1177/2042098611415567.
    1. Badger V.O., Ledeboer N.A., Graham M.B., Edmiston C.E., Jr. Clostridium difficile: Epidemiology, pathogenesis, management, and prevention of a recalcitrant healthcare-associated pathogen. JPEN J. Parenter. Enteral. Nutr. 2012;36:645–662. doi: 10.1177/0148607112446703.
    1. Cain G.D., Reiner E.B., Patterson M. Effects of neomycin on disaccharidase activity of the small bowel. Arch. Intern. Med. 1968;122:311–341. doi: 10.1001/archinte.1968.00300090021004.
    1. Kaltenbach G., Heitz D. Antibiotic-associated diarrhea in the elderly. Rev. Med. Interne. 2004;25:46–53. doi: 10.1016/j.revmed.2003.10.002.
    1. Zhang W., Zhu B., Xu J., Liu Y., Qiu E., Li Z., Li Z., He Y., Zhou H., Bai Y., et al. Bacteroides fragilis Protects Against Antibiotic-Associated Diarrhea in Rats by Modulating Intestinal Defenses. Front Immunol. 2018;9:1040. doi: 10.3389/fimmu.2018.01040.
    1. Stein A. Chemotherapy-induced diarrhea: Pathophysiology, frequency and guideline-based management. Ther. Adv. Med. Oncol. 2010;2:51–63. doi: 10.1177/1758834009355164.
    1. Andreyev J., Ross P., Donnellan C., Lennan E., Leonard P., Waters C., Wedlake L., Bridgewater J., Glynne-Jones R., Allum W., et al. Guidance on the management of diarrhoea during cancer chemotherapy. Lancet Oncol. 2014;15:e447–e460. doi: 10.1016/S1470-2045(14)70006-3.
    1. Philip N.A., Ahmed N., Pitchumoni C.S. Spectrum of Drug-induced Chronic Diarrhea. J. Clin. Gastroenterol. 2017;51:111–117. doi: 10.1097/MCG.0000000000000752.
    1. Bowen J.M. Mechanisms of TKI-induced diarrhea in cancer patients. Curr, Opin. Support Palliat. Care. 2013;7 doi: 10.1097/SPC.0b013e32835ec861.
    1. Davis J.S., Lee H.Y., Kim J., Advani S.M., Peng H.L., Banfield E., Hawk E.T., Chang S., Frazier-Wood A.C. Use of non-steroidal anti-inflammatory drugs in US adults: Changes over time and by demographic. Open Heart. 2017;4:e000550. doi: 10.1136/openhrt-2016-000550.
    1. Gómez-Acebo I., Dierssen-Sotos T., de Pedro M., Pérez-Gómez B., Castaño-Vinyals G., Fernández-Villa T., Palazuelos-Calderón C., Amiano P., Etxeberria J., Benavente Y., et al. Epidemiology of non-steroidal anti-inflammatory drugs consumption in Spain. The MCC-Spain study. BMC Public Health. 2018;18:1134. doi: 10.1186/s12889-018-6019-z.
    1. Jerez-Roig J., Medeiros L.F., Silva V.A., Bezerra C.L., Cavalcante L.A., Piuvezam G., Souza D.L. Prevalence of self-medication and associated factors in an elderly population: A systematic review. Drugs Aging. 2014;31:883–896. doi: 10.1007/s40266-014-0217-x.
    1. Morgan G.J., Poland M., DeLapp R.E. Efficacy and safety of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in the elderly. Am. J. Med. 1993;95:19S–27S. doi: 10.1016/0002-9343(93)90392-3.
    1. Fradkin A., Yahav J., Zemer D., Jonas A. Colchicine-induced lactose malabsorption in patients with familial Mediterranean fever. Isr. J. Med. Sci. 1995;31:616–620.
    1. Roder C., Thomson M.J. Auranofin: Repurposing an old drug for a golden new age. Drugs RD. 2015;15:13–20. doi: 10.1007/s40268-015-0083-y.
    1. Pasricha P.J. Treatment of disorders of bowel motility and water flux; antiemetics: Agents used in biliary and pancreatic disease. In: Brunton L.L., editor. Goodman & Gilman’s the Pharmacological Basis of Therapeutics. McGraw Hill; New York, NY, USA: 2006. pp. 983–1008.
    1. Malik E.M., Müller C.E. Anthraquinones As Pharmacological Tools and Drugs. Med. Res. Rev. 2016;36:705–748. doi: 10.1002/med.21391.
    1. Fidelix T.S., Soares B.G., Trevisani V.F. Diacerein for osteoarthritis. Cochrane Database Syst Rev. 2006;25
    1. Fidelix T.S., Macedo C.R., Maxwell L.J., Fernandes Moça Trevisani V. Diacerein for osteoarthritis. Cochrane Database Syst. Rev. 2014 doi: 10.1002/14651858.CD005117.pub3.
    1. Pelletier J.P., Martel-Pelletier J. Diacerein-containing products: Same risk of diarrhoea? Aging Clin. Exp. Res. 2018;30:411–412. doi: 10.1007/s40520-018-0911-3.
    1. PRAC Recommends Suspension of Diacerein-Containing Medicines. [(accessed on 21 January 2019)]; Available online: .
    1. Brooks D.J. Optimizing levodopa therapy for Parkinson’s disease with levodopa/carbidopa/entacapone: Implications from a clinical and patient perspective. Neuropsychiatr. Dis. Treat. 2008;4:39–47. doi: 10.2147/NDT.S1660.
    1. Kaakkola S. Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson’s disease. Int. Rev. Neurobiol. 2010;95:207–225.
    1. Kaakkola S. Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson’s disease. Drugs. 2000;59:1233–1250. doi: 10.2165/00003495-200059060-00004.
    1. Roehr J., Woods A., Corbett R., Kongsamut S. Changes in paroxetine binding in the cerebral cortex of polydipsic rats. Eur. J. Pharmacol. 1995;278:75–78. doi: 10.1016/0014-2999(95)00099-7.
    1. Jacob S., Spinler S.A. Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann. Pharmacother. 2006;40:1618–1622. doi: 10.1345/aph.1G293.
    1. Langan J., Martin D., Shajahan P., Smith D. Antipsychotic dose escalation as a trigger for neuroleptic malignant syndrome (NMS): Literature review and case series report. BMC Psychiatry. 2012;29:214. doi: 10.1186/1471-244X-12-214.
    1. Millson R.C., Emes C.E., Glackman W.G. Self-induced water intoxication treated with risperidone. Can. J. Psychiatry. 1996;41:648–650. doi: 10.1177/070674379604101008.
    1. Kawai N., Baba A., Suzuki T. Risperidone failed to improve polydipsia-hyponatremia of the schizophrenic patients. Psychiatry Clin. Neurosci. 2002;56:107–110. doi: 10.1046/j.1440-1819.2002.00937.x.
    1. Kruse D., Pantelis C., Rudd R., Quek J., Herbert P., McKinley M. Treatment of psychogenic polydipsia: Comparison of risperidone and olanzapine, and the effects of an adjunctive angiotensin-II receptor blocking drug (irbesartan) Aust. N. Z. J. Psychiatry. 2001;35:65–68. doi: 10.1046/j.1440-1614.2001.00847.x.
    1. Yamaguchi K., Hama H. Changes in vasopressin release and autonomic function induced by manipulating forebrain GABAergic signaling under euvolemia and hypovolemia in conscious rats. Endocr. J. 2011;58:559–573. doi: 10.1507/endocrj.K11E-002.
    1. Vgontzas A.N., Mastorakos G., Bixler E.O., Kales A., Gold P.W., Chrousos G.P. Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes: Potential clinical implications. Clin. Endocrinol (Oxf) 1999;51:205–215. doi: 10.1046/j.1365-2265.1999.00763.x.
    1. Schulze J.D., Ashiru D.A., Khela M.K., Evans D.F., Patel R., Parsons G.E., Coffin M.D., Basit A.W. Impact of formulation excipients on human intestinal transit. J. Pharm. Pharmacol. 2006;58:821–825. doi: 10.1211/jpp.58.6.0012.
    1. Hill D.B., Henderson L.M., McClain C.J. Osmotic diarrhea induced by sugar-free theophylline solution in critically ill patients. JPEN J. Parenter. Enteral. Nutr. 1991;15:332–336. doi: 10.1177/0148607191015003332.
    1. Bayraktar Ekincioglu A., Demirkan K. Awareness of Healthcare Professionals About Sorbitol-Related Diarrhea in Pediatrics. Yogun. Bakim. Derg. 2017;8:14–18. doi: 10.5152/dcbybd.2017.1454.
    1. Adkin D.A., Davis S.S., Sparrow R.A., Huckle P.D., Phillips A.J., Wilding I.R. The effect of different concentrations of mannitol in solution on small intestinal transit: Implications for drug absorption. Pharm. Res. 1995;12:393–396. doi: 10.1023/A:1016256619309.
    1. Hammer H.F., Santa Ana C.A., Schiller L.R., Fordtran J.S. Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose. J. Clin. Investig. 1989;84:1056–1062. doi: 10.1172/JCI114267.
    1. Dahlgren D., Roos C., Johansson P., Tannergren C., Lundqvist A., Langguth P., Sjöblom M., Sjögren E., Lennernäs H. The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs. Int. J. Pharm. 2018;547:158–168. doi: 10.1016/j.ijpharm.2018.05.029.
    1. Dahlgren D., Roos C., Lundqvist A., Tannergren C., Langguth P., Sjöblom M., Sjögren E., Lennernäs H. Preclinical Effect of Absorption Modifying Excipients on Rat Intestinal Transport of Model Compounds and the Mucosal Barrier Marker 51Cr-EDTA. Mol. Pharm. 2017;14:4243–4251. doi: 10.1021/acs.molpharmaceut.7b00353.
    1. Heade J., Maher S., Bleiel S.B., Brayden D.J. Labrasol® and Salts of Medium-Chain Fatty Acids Can Be Combined in Low Concentrations to Increase the Permeability of a Macromolecule Marker Across Isolated Rat Intestinal Mucosae. J. Pharm. Sci. 2018;107:1648–1655. doi: 10.1016/j.xphs.2018.02.012.
    1. Varum F.J., Merchant H.A., Basit A.W. Oral modified-release formulations in motion: The relationship between gastrointestinal transit and drug absorption. Int. J. Pharm. 2010;395:26–36. doi: 10.1016/j.ijpharm.2010.04.046.
    1. Schulze J.D., Waddington W.A., Eli P.J., Parsons G.E., Coffin M.D., Basit A.W. Concentration-dependent effects of polyethylene glycol 400 on gastrointestinal transit and drug absorption. Pharm. Res. 2003;20:1984–1988. doi: 10.1023/B:.
    1. Basit A.W., Newton J.M., Short M.D., Waddington W.A., Ell P.J., Lacey L.F. The effect of polyethylene glycol 400 on gastrointestinal transit: Implications for the formulation of poorly-water soluble drugs. Pharm. Res. 2001;18:1146–1150. doi: 10.1023/A:1010927026837.
    1. Basit A.W., Podczeck F., Newton J.M., Waddington W.A., Ell P.J., Lacey L.F. Influence of polyethylene glycol 400 on the gastrointestinal absorption of ranitidine. Pharm. Res. 2002;19:1368–1374. doi: 10.1023/A:1020315228237.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel