Effects of obesity on the pharmacology of proton pump inhibitors: current understanding and future implications for patient care and research

References

• Strand DS, Kim D, Peura DA. 25 Years of Proton Pump inhibitors: a comprehensive review. Gut Liver. 2017;11(1):27–37.
   PubMed Web of Science ®Google Scholar
• Kalichman L, Livshits G, Kobyliansky E. Indices of body composition and chronic morbidity: a cross-sectional study of a rural population in central Russia. Am J Hum Biol. 2006;18(3):350–358.
   PubMed Web of Science ®Google Scholar
• Boylan MR, Khalili H, Huang ES, et al. Measures of adiposity are associated with increased risk of peptic ulcer. Clin Gastroenterol Hepatol. 2014;12(10):1688–1694.
   PubMed Web of Science ®Google Scholar
• Weatherall R, Shaper AG. Overweight and obesity in middle-aged British men. Eur J Clin Nutr. 1988;42(3):221–231.
   PubMed Web of Science ®Google Scholar
• Kim J, Kim KH, Lee BJ. Association of peptic ulcer disease with obesity, nutritional components, and blood parameters in the Korean population. PLoS One. 2017;12(8):e0183777.
   PubMed Web of Science ®Google Scholar
• El-Serag HB, Graham DY, Satia JA, et al. Obesity is an independent risk factor for GERD symptoms and erosive esophagitis. Am J Gastroenterol. 2005;100(6):1243–1250.
   PubMed Web of Science ®Google Scholar
• Malaty HM, Fraley JK, Abudayyeh S, et al. Obesity and gastroesophageal reflux disease and gastroesophageal reflux symptoms in children. Clin Exp Gastroenterol. 2009;2:31–36.
   PubMedGoogle Scholar
• Freedman DS. Centers for Disease C, Prevention. Obesity - United States, 1988-2008. MMWR Suppl. 2011;60(1):73–77.
   PubMedGoogle Scholar
• Lovegrove C. Obesity is linked with increased risk of gastroesophageal reflux disease. Nat Clin Pract Gastroenterol Hepatol. 2005;2(11):501.
   Google Scholar
• Lima JJ, Thomas CD, Barbarino J, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C19 and proton pump inhibitor dosing. Clin Pharmacol Ther. 2021;109(6):1417–1423.
   PubMed Web of Science ®Google Scholar
• Benmassaoud A, McDonald EG, Lee TC. Potential harms of proton pump inhibitor therapy: rare adverse effects of commonly used drugs. Cmaj. 2016;188(9):657–662.
   PubMed Web of Science ®Google Scholar
• Smit C, De Hoogd S, Bruggemann RJM, et al. Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Expert Opin Drug Metab Toxicol. 2018;14(3):275–285.
   PubMed Web of Science ®Google Scholar
• Abdelaal M, le Roux CW, Docherty NG. Morbidity and mortality associated with obesity. Ann Transl Med. 2017;5(7):161.
   PubMed Web of Science ®Google Scholar
• WHO. Obesity and overweight 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
   Google Scholar
• Prevention CfDCa. Defining adult overweight and obesity 2022. Available from: https://www.cdc.gov/obesity/basics/adult-defining.html
   Google Scholar
• Prevention CfDCa. Defining childhood weight status 2022. Available from: https://www.cdc.gov/obesity/basics/childhood-defining.html
   Google Scholar
• Chang P, Friedenberg F. Obesity and GERD. Gastroenterol Clin North Am. 2014;43(1):1417–1423.
   Web of Science ®Google Scholar
• El-Serag HB, Ergun GA, Pandolfino J, et al. Obesity increases oesophageal acid exposure. Gut. 2007;56(6):749–755.
   PubMed Web of Science ®Google Scholar
• Pandolfino JE, El–Serag HB, Zhang Q, et al. Obesity: a challenge to esophagogastric junction integrity. Gastroenterology. 2006;130(3):639–649.
   PubMed Web of Science ®Google Scholar
• de Vries DR, van Herwaarden MA, Smout AJ, et al. Gastroesophageal pressure gradients in gastroesophageal reflux disease: relations with hiatal hernia, body mass index, and esophageal acid exposure. Am J Gastroenterol. 2008;103(6):1349–1354.
   PubMed Web of Science ®Google Scholar
• Shah SL, Lacy BE, DiBaise JK, et al. The impact of obesity on oesophageal acid exposure time on and off proton pump inhibitor therapy. Aliment Pharmacol Ther. 2015;42(9):1093–1100.
   PubMed Web of Science ®Google Scholar
• Shakhnovich V, Smith PB, Guptill JT, et al. Obese children require lower doses of pantoprazole than nonobese peers to achieve equal systemic drug exposures. J Pediatr. 2018;193:102–108 e1.
   PubMed Web of Science ®Google Scholar
• Gerhart JG, Carreno FO, Edginton AN, et al. Development and evaluation of a virtual population of children with obesity for physiologically based pharmacokinetic modeling. Clin Pharmacokinet. 2022;61(2):307–320.
   PubMed Web of Science ®Google Scholar
• Berton M, Bettonte S, Stader F, et al. Repository describing the anatomical, physiological, and biological changes in an obese population to inform physiologically based pharmacokinetic models. Clin Pharmacokinet. 2022;61(9):1251–1270.
   PubMed Web of Science ®Google Scholar
• Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2021;143(21):e984–e1010.
   PubMed Web of Science ®Google Scholar
• Knibbe CA, Brill MJ, van Rongen A, et al. Drug disposition in obesity: toward evidence-based dosing. Annu Rev Pharmacol Toxicol. 2015;55:149–167.
   PubMed Web of Science ®Google Scholar
• Krogstad V, Peric A, Robertsen I, et al. Correlation of body weight and composition with hepatic activities of cytochrome p450 enzymes. J Pharm Sci. 2021;110(1):432–437.
   PubMed Web of Science ®Google Scholar
• Ulvestad M, Skottheim IB, Jakobsen GS, et al. Impact of OATP1B1, MDR1, and CYP3A4 expression in liver and intestine on interpatient pharmacokinetic variability of atorvastatin in obese subjects. Clin Pharmacol Ther. 2013;93(3):275–282.
   PubMed Web of Science ®Google Scholar
• Teixeira TF, Souza NC, Chiarello PG, et al. Intestinal permeability parameters in obese patients are correlated with metabolic syndrome risk factors. Clin Nutr. 2012;31(5):735–740.
   PubMed Web of Science ®Google Scholar
• Asad Mansoor NM. Volume of Distribution: StatPearls; 2022 [cited 2022]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545280/
   Google Scholar
• Kocz AZGSBPR. Drug elimination: StatPearls; 2022 [cited 2022]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547662/
   Google Scholar
• Preuss. STSCV. drug metabolism: StatPearls; 2022 [cited 2022]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK442023/
   Google Scholar
• Chen K, Luo P, Yang G, et al. Population pharmacokinetics of omeprazole in obese and normal-weight adults. Expert Rev Clin Pharmacol. 2022;15(4):461–471.
   PubMed Web of Science ®Google Scholar
• Shakhnovich V, Brian Smith P, Guptill JT, et al. A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents. Paediatr Drugs. 2018; 20(5):483–495.
   PubMed Web of Science ®Google Scholar
• Kovesdy CP, Furth SL, Zoccali C, et al. Obesity and kidney disease: hidden consequences of the epidemic. Can J Kidney Health Dis. 2017;4:2054358117698669.
   Google Scholar
• Moreno-Navarrete JM, Ortega FJ, Rodriguez-Hermosa JI, et al. OCT1 expression in adipocytes could contribute to increased metformin action in obese subjects. Diabetes. 2011;60(1):168–176.
   PubMed Web of Science ®Google Scholar
• Neely M, Jelliffe R. Practical, individualized dosing: 21st century therapeutics and the clinical pharmacometrician. J Clin Pharmacol. 2010;50(7):842–847.
   PubMed Web of Science ®Google Scholar
• Neely M, Jelliffe R. Practical therapeutic drug management in HIV-infected patients: use of population pharmacokinetic models supplemented by individualized Bayesian dose optimization. J Clin Pharmacol. 2008;48(9):1081–1091.
   PubMed Web of Science ®Google Scholar
• Peck RW, Shahin MH, Vinks AA. Precision dosing: the clinical pharmacology of goldilocks. Clin Pharmacol Ther. 2021;109(1):11–14.
   PubMed Web of Science ®Google Scholar
• Vaughns JD, Conklin LS, Long Y, et al. Obesity and pediatric drug development. J Clin Pharmacol. 2018;58(5):650–661.
   PubMed Web of Science ®Google Scholar
• Must A, Anderson SE. Body mass index in children and adolescents: considerations for population-based applications. Int J Obes (Lond). 2006;30(4):590–594.
   PubMed Web of Science ®Google Scholar
• Harskamp-van Ginkel MW, Hill KD, Becker KC, et al. Drug dosing and pharmacokinetics in children with obesity: a systematic review. JAMA Pediatr. 2015;169(7):678–685.
   PubMed Web of Science ®Google Scholar
• Luo L, Liu M. Adipose tissue in control of metabolism. J Endocrinol. 2016;231(3):R77–R99.
   PubMed Web of Science ®Google Scholar
• Shakhnovich V, Abdel-Rahman S, Friesen CA, et al. Lean body weight dosing avoids excessive systemic exposure to proton pump inhibitors for children with obesity. Pediatr Obes. 2019; 14(1):e12459.
   Web of Science ®Google Scholar
• Shin JM, Kim N. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors. J Neurogastroenterol Motil. 2013;19(1):25–35.
   PubMed Web of Science ®Google Scholar
• Brill MJ, Diepstraten J, van Rongen A, et al. Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet. 2012;51(5):277–304.
   PubMed Web of Science ®Google Scholar
• Shakhnovich V, Abdel-Rahman S, Chan S, et al. American Society for Clinical Pharmacology and Therapeutics. Clin. Pharmacol. Ther. 2021;109:S5–S88.
   PubMed Web of Science ®Google Scholar
• de Jong LM, Jiskoot W, Swen JJ, et al. Distinct effects of inflammation on cytochrome P450 regulation and drug metabolism: lessons from experimental models and a potential role for pharmacogenetics. Genes (Basel). 2020;11:12.
   Web of Science ®Google Scholar
• Christensen H, Hermann M. Immunological response as a source to variability in drug metabolism and transport. Front Pharmacol. 2012;3:8.
   PubMed Web of Science ®Google Scholar
• Chen WY, Chang WL, Tsai YC, et al. Double-dosed pantoprazole accelerates the sustained symptomatic response in overweight and obese patients with reflux esophagitis in Los Angeles grades A and B. Am J Gastroenterol. 2010;105(5):1046–1052.
   PubMed Web of Science ®Google Scholar
• Belhocine K, Vavasseur F, Volteau C, et al. Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole. BMC Gastroenterol. 2014;14:128.
   PubMed Web of Science ®Google Scholar
• Luo JY, Niu CY, Wang XQ, et al. Effect of a single oral dose of rabeprazole on nocturnal acid breakthrough and nocturnal alkaline amplitude. World J Gastroenterol. 2003;9(11):2583–2586.
   PubMed Web of Science ®Google Scholar
• Sheu BS, Cheng HC, Chang WL, et al. The impact of body mass index on the application of on-demand therapy for Los Angeles grades A and B reflux esophagitis. Am J Gastroenterol. 2007;102(11):2387–2394.
   PubMed Web of Science ®Google Scholar
• Sheu B-S, Chang W-L, Cheng H-C, et al. Body mass index can determine the healing of reflux esophagitis with los angeles grades C and D by Esomeprazole. Am J Gastroenterol. 2008;103(9):2209–2214.
   PubMed Web of Science ®Google Scholar
• Portoles-Perez A, Paterna ABR, Sanchez Pernaute A, et al. Effect of obesity and roux-en-y gastric surgery on omeprazole pharmacokinetics. Obes Facts. 2022;15(2):271–280.
   PubMed Web of Science ®Google Scholar
• Mitrov-Winkelmolen L, van Buul-Gast MW, Swank DJ, et al. The Effect of Roux-en-Y Gastric Bypass Surgery in Morbidly Obese Patients on Pharmacokinetics of (Acetyl)Salicylic Acid and Omeprazole: the ERY-PAO Study. Obes Surg. 2016;26(9):2051–2058.
   PubMed Web of Science ®Google Scholar
• Kvitne KE, Krogstad V, Wegler C, et al. Short- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activity. Br J Clin Pharmacol. 2022;88(9):4121–4133.
   PubMed Web of Science ®Google Scholar
• Lima JJ, Lang JE, Mougey EB, et al. Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children. J Pediatr. 2013;163(3):686–691.
   PubMed Web of Science ®Google Scholar
• Cicali EJ, Blake K, Gong Y, et al. Novel Implementation of Genotype-Guided Proton Pump Inhibitor Medication Therapy in Children: a Pilot, Randomized, Multisite Pragmatic Trial. Clin Transl Sci. 2019;12(2):172–179.
   PubMed Web of Science ®Google Scholar
• Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007;102(9):2047–2056. quiz 2057.
   PubMed Web of Science ®Google Scholar
• Kwok CS, Arthur AK, Anibueze CI, et al. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107(7):1011–1019.
   PubMed Web of Science ®Google Scholar
• Janarthanan S, Ditah I, Adler DG, et al. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol. 2012;107(7):1001–1010.
   PubMed Web of Science ®Google Scholar
• Law EH, Badowski M, Hung YT, et al. Association Between Proton Pump Inhibitors and Microscopic Colitis. Ann Pharmacother. 2017;51(3):253–263.
   PubMed Web of Science ®Google Scholar
• Verhaegh BP, de Vries F, Masclee AA, et al. High risk of drug-induced microscopic colitis with concomitant use of NSAIDs and proton pump inhibitors. Aliment Pharmacol Ther. 2016;43(9):1004–1013.
   PubMed Web of Science ®Google Scholar
• Willems RPJ, van Dijk K, Ket JCF, et al. Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms: a Systematic Review and Meta-analysis. JAMA Intern Med. 2020;180(4):561–571.
   PubMed Web of Science ®Google Scholar
• Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med. 1994;120(3):211–215.
   PubMed Web of Science ®Google Scholar
• Lam JR, Schneider JL, Zhao W, et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435–2442.
   PubMed Web of Science ®Google Scholar
• Hess MW, Hoenderop JG, Bindels RJ, et al. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther. 2012;36(5):405–413.
   PubMed Web of Science ®Google Scholar
• Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, et al. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail. 2015;37(7):1237–1241.
   PubMed Web of Science ®Google Scholar
• Ajmera AV, Shastri GS, Gajera MJ, et al. Suboptimal response to ferrous sulfate in iron-deficient patients taking omeprazole. Am J Ther. 2012;19(3):185–189.
   PubMed Web of Science ®Google Scholar
• Hutchinson C, Geissler CA, Powell JJ, et al. Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut. 2007;56(9):1291–1295.
   PubMed Web of Science ®Google Scholar
• McColl KE. Effect of proton pump inhibitors on vitamins and iron. Am J Gastroenterol. 2009;104(Suppl 2):S5–9.
   PubMed Web of Science ®Google Scholar
• Tuukkanen J, Vaananen HK. Omeprazole, a specific inhibitor of H+-K+-ATPase, inhibits bone resorption in vitro. Calcif Tissue Int. 1986;38(2):123–125.
   PubMed Web of Science ®Google Scholar
• Mizunashi K, Furukawa Y, Katano K, et al. Effect of omeprazole, an inhibitor of H+,K(+)-ATPase, on bone resorption in humans. Calcif Tissue Int. 1993;53(1):21–25.
   PubMed Web of Science ®Google Scholar
• Sampathkumar K, Ramalingam R, Prabakar A, et al. Acute interstitial nephritis due to proton pump inhibitors. Indian J Nephrol. 2013;23(4):304–307.
   PubMedGoogle Scholar
• Ra A, Tobe SW. Acute interstitial nephritis due to pantoprazole. Ann Pharmacother. 2004;38(1):41–45.
   PubMed Web of Science ®Google Scholar
• Muriithi AK, Leung N, Valeri AM, et al. Biopsy-proven acute interstitial nephritis, 1993-2011: a case series. Am J Kidney Dis. 2014;64(4):558–566.
   PubMed Web of Science ®Google Scholar
• Kwok CS, Yeong JK, Loke YK. Meta-analysis: risk of fractures with acid-suppressing medication. Bone. 2011;48(4):768–776.
   PubMed Web of Science ®Google Scholar
• Freedberg DE, Haynes K, Denburg MR, et al. Use of proton pump inhibitors is associated with fractures in young adults: a population-based study. Osteoporos Int. 2015;26(10):2501–2507.
   PubMed Web of Science ®Google Scholar
• Stark CM, Nylund CM. Side effects and complications of proton pump inhibitors: a pediatric perspective. J Pediatr. 2016;168:16–22.
   PubMed Web of Science ®Google Scholar
• Chung EY, Yardley J. Are there risks associated with empiric acid suppression treatment of infants and children suspected of having gastroesophageal reflux disease? Hosp Pediatr. 2013;3(1):16–23.
   PubMedGoogle Scholar
• Chen Y-H, Lin K-H, Wang H-M, et al. The efficacies of esomeprazole- versus pantoprazole-based reverse hybrid therapy for Helicobacter pylori eradication. Adv Dige Med. 2018;5(1–2): 26–32
   Web of Science ®Google Scholar
• Hosey CM, Halpin K, Shakhnovich V, et al. Pediatric growth patterns in youth-onset type 2 diabetes mellitus: implications for physiologically-based pharmacokinetic models. Clin Transl Sci. 2022;15(4):912–922.
   PubMed Web of Science ®Google Scholar