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Pharmacokinetics of intravenous omeprazole in critically ill paediatric patients

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Abstract

The proton pump inhibitors are first-line drugs for the treatment of a number of gastrointestinal diseases. These drugs have a good safety profile, making it possible to use them in paediatric patients. Although their pharmacokinetics in children has not been extensively studied, research performed suggests that the dose used should be varied as a function of age, as this factor affects the drug’s metabolism. Proton pump inhibitors can be used in critically ill children for the prophylaxis and treatment of gastrointestinal haemorrhage, although there is still little experience with this. The most widely used proton pump inhibitor at the present time is omeprazole. As there are specific characteristics of these patients that could alter the pharmacokinetics of the drugs, studies need to be performed to determine the most suitable dose and dosage interval.

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References

  1. Der G (2003) An overview of proton pump inhibitors. Gastroenterol Nurs 26:182–190

    Article  PubMed  Google Scholar 

  2. Robinson M, Horn J (2003) Clinical pharmacology of proton pump inhibitors. What the practising physician needs to know. Drugs 63:2739–2754

    Article  CAS  PubMed  Google Scholar 

  3. Vanderhoff BT, Tahboub RM (2002) Proton pump inhibitors, an update. Clin Pharmacol 66:273–280

    Google Scholar 

  4. Pongprasobchai S, Kridkratoke S, Nopmaneejumruslers C (2009) Proton pump inhibitors for the prevention of stress-related mucosal disease in critically-ill patients, a meta-analysis. J Med Assoc Thai 92:632–637

    PubMed  Google Scholar 

  5. Savarino V, Di Mario F, Scarpignato C (2009) Proton pump inhibitors in GORD. An overview of their pharmacology, efficacy and safety. Pharmacol Res 59:135–153

    Article  CAS  PubMed  Google Scholar 

  6. Gibbons TE, Gold BD (2003) The use of proton pumps inhibitors in children. A comprehensive review. Pediatr Drugs 5:25–40

    Google Scholar 

  7. Litalien C, Theoret Y, Faure C (2005) Pharmacokinetics of proton pump inhibitors in children. Clin Pharmacokinet 44:441–466

    Article  CAS  PubMed  Google Scholar 

  8. Sachs G, Shin JM, Briving C, Wallmark B, Hersey S (1995) The pharmacology of the gastric acid pump: the H+, K+ ATPase. Annu Rev Pharmacol Toxicol 35:277–305

    Article  CAS  PubMed  Google Scholar 

  9. Shi S, Klotz U (2008) Proton pump inhibitors, an update of their clinical use and pharmacokinetics. Eur J Clin Pharmacol 64:935–951

    Article  CAS  PubMed  Google Scholar 

  10. Kearns GL, Winter HS (2003) Proton pump inhibitors in pediatrics, relevant pharmacokinetics and pharmacodynamics. J Pediatr Gastroenterol Nutr 37:52–59

    Article  Google Scholar 

  11. Furuta T, OACI K, Kosuge K, Zhao XJ, Takashima M, Kimura M, Nishimoto M, Hanahi H, Kaneko E, Ishizaki T (1999) CYP 2C19 genotype status and effect of omeprazole on intragastric pH in humans. Clin Pharmacol Ther 65:552–561

    Article  CAS  PubMed  Google Scholar 

  12. Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, Ingelman-Sundberg M (2006) A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 79:103–113

    Article  CAS  PubMed  Google Scholar 

  13. Zimmermann AE, Walters K, Katona BG, Souney PF, Levine D (2001) A review of omeprazol use in the treatment of acid-related disorders in children. Clin Ther 23:660–679

    Article  CAS  PubMed  Google Scholar 

  14. Boyle JT (2003) Acid secretion from birth to adulthood. J Pediatr Gastroenterol Nutr 37:12–16

    Article  Google Scholar 

  15. Marier JF, Dubuc MC, Drouin E, Alvarez F, Ducharme MP, Brazier JL (2004) Pharmacokinetics of omeprazole in healthy adults and in children with gastroesophageal reflux disease. Ther Drug Monit 26:3–8

    Article  CAS  PubMed  Google Scholar 

  16. Wyllie R (2004) Stomach and bowel: normal development, structure and function. In: Behrman RE, Kliegman RM, Hal B (eds) The Nelson textbook, 17th ed. Saunders, Madrid, pp 1228–1229

    Google Scholar 

  17. Ginsberg G, Hattis D, Miller R, Sonawane B (2004) Pediatric pharmacokinetic data, Implications for environmental risk assessment for children. Pediatrics 113:973–983

    PubMed  Google Scholar 

  18. Kearns GL, Andersson T, James LP, Gaedigk A, Kraynak RA, Abdel-Rahman SM, Ramabadran K, van den Anker JN (2003) Omeprazole disposition in children following single-dose administration. J Clin Pharmacol 43:840–848

    Article  CAS  PubMed  Google Scholar 

  19. Leeder JS, Kearns GL (1997) Pharmacogenetics in pediatrics. Implications for practice. Pediatr Clin North Am 44:55–77

    Article  CAS  PubMed  Google Scholar 

  20. Page CP, Curtis MJ, Sutter MC, Walker MJA, Hoffman BB (1998) Pharmacology integrated. Medical, Madrid

    Google Scholar 

  21. Andersson T, Hassall E, Lundborg P, Shepherd R, Radke M, Marcon M, Dalväg A, Martin S, Behrens R, Koletzko S, Becker M, Drouin E, Göthberg G (2000) Pharmacokinetics of orally administered omeprazole in children. Am J Gastroenterol 95:3101–3106

    Google Scholar 

  22. Andersson T, Gothberg G, Friberg L, Gatzinsky V, Lundborg P, Rosen E (2001) Pharmacokinetics of intravenous omeprazole in neonates and infants. J Pediatr Gastroenterol Nutr 33:424 [abstract]

    Google Scholar 

  23. Jaqz-Aigrain E, Bellaich M, Faure C, Navarro J, Rohrlich P, Baudouin V (1994) Pharmacokinetics of intravenous omeprazole in children. Eur J Pharmacol 47:181–185

    Google Scholar 

  24. Faure C, Michaud L, Khan Shaghaghi E, Popon M, Turck D, Navarro J, Jaqz-Aigrain E (2001) Intravenous omeprazole in children. Pharmacokinetics and effect on 24-hour intragastric pH. J Pediatr Gastroenterol Nutr 33:144–148

    Article  CAS  PubMed  Google Scholar 

  25. Brett S (2005) Science review. The use of proton pump inhibitors for gastric acid suppression in critical illness. Crit Care 9:45–50

    Article  PubMed  Google Scholar 

  26. Lugo R, Harrison M, Cash J, Sweeley J, Vernon DD (2001) Pharmacokinetics and pharmacodynamics of ranitidine in critically ill children. Crit Care Med 29:759–764

    Article  CAS  PubMed  Google Scholar 

  27. Boucher BA, Wood GC, Swanson JM (2006) Pharmacokinetic changes in critical illness. Crit Care Clin 22:255–271

    Article  CAS  PubMed  Google Scholar 

  28. Ecknauer R, Sircar B, Johnson LR (1981) Effect of dietary bulk on small intestinal morphology and cell renewal in the rat. Gastroenterology 81:781–786

    CAS  PubMed  Google Scholar 

  29. Levine GM, Deren JJ, Steiger E, Zinno R (1974) Role of oral intake in maintenance of gut mass and disaccharide activity. Gastroenterology 67:975–982

    CAS  PubMed  Google Scholar 

  30. Martyn JA, Abernethy DR, Greenblatt DJ (1984) Plasma protein binding of drugs after severe burn injury. Clin Pharmacol Ther 35:535–539

    CAS  PubMed  Google Scholar 

  31. Edwars DJ, Lalka D, Cerra F, Slaughter RL (1982) Alpaa1-acid glycoprotein concentration and protein binding in trauma. Clin Pharmacol Ther 31:62–67

    Google Scholar 

  32. Meier-Hellmann A, Reinhart K, Bredle DJ, Bredle DL, Specht M, Spies C, Hannemann L (1997) Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med 25:399–404

    Article  CAS  PubMed  Google Scholar 

  33. McKindley DS, Hanes SD, Boucher BA (1998) Hepatic drug metabolism in critical illness. Pharmacotheraphy 18:759–778

    CAS  Google Scholar 

  34. Cedeberg C, Thomson AB, Mahachai V, Westin JA, Kirdeikis P, Fisher D, Zuk L, Marriage B (1992) Effect of intravenous and oral omeprazole on 24-hour intragastric acidity in duodenal ulcer patients. Gastroenterology 103:913–918

    Google Scholar 

  35. Cedeberg C, Röhss K, Lundborg P, Olbe L (1993) Effect of once daily intravenous and oral omeprazole on 24-hour intragastric acidity in healthy subjects. Scand J Gastroenterol 28:179–184

    Article  Google Scholar 

  36. Piqué JM, Feu F, de Prada G, Röhss K, Hasselgren G (2002) Pharmacokinetics of omeprazole given by continuous intravenous infusion to patients with varying degrees of hepatic dysfunction. Clin Pharmacokinet 41:999–1004

    Article  PubMed  Google Scholar 

  37. Simon-Rudler M, Massard J, Bernard-Chabert B, Di Martino V, Ratziu V, Poynard T, Thabut D (2007) Continuous infusion of high-dose omeprazole is more effective than standard-dose omeprazole in patients with high-risk peptic ulcer bleeding, a retrospective study. Aliment Pharmacol Ther 25:994–954

    Google Scholar 

  38. López-Herce J, Dorao P, Elola P, Delgado M, Ruza F, Madero R (1992) Frequency and prophylaxis of upper gastrointestinal haemorrhage in critically ill children, a prospective study comparing the efficacy of almagate, ranitidine and sucralfate. Crit Care Med 20:1082–1089

    Article  PubMed  Google Scholar 

  39. Maki M, Ruuska T, Kuusela AL, Karikoski-leo R, Ikonen RS (1993) High prevalence of asymptomatic esophageal and gastric lesions in preterm infants in intensive care. Crit Care Med 21:1863–1867

    CAS  PubMed  Google Scholar 

  40. Kaufman SS, Lyden ER, Brown CR, Davis CK, Andersen DA, Olsen KM, Bergman KL, Horslen SP, Sudan DL, Fox IJ, Shaw BW, Langnas AN (2002) Omeprazole therapy in pediatric patients after liver and intestinal transplantation. J Pediatr Gastroenterol Nutr 34:194–198

    Article  CAS  PubMed  Google Scholar 

  41. Cook DJ, Fuller HD, Guyatt GH, Marshall JC, Leasa D, Hall R, Winton TL, Rutledge F, Todd TJR, Roy P, Lacroix J, Griffith L, Willian A (1994) Risk factors for gastrointestinal bleeding in critically ill patients. N Engl J Med 330:377–381

    Article  CAS  PubMed  Google Scholar 

  42. Nithiwathanapong C, Reungrongrat S, Ukarapol N (2005) Prevalence and risk factors of stress-induced gastrointestinal bleeding in critically ill children. World J Gastroenterol 11:6839–6842

    PubMed  Google Scholar 

  43. Pea F, Pavan F, Furlanut M (2008) Clinical relevance of pharmacokinetics and pharmacodynamics in cardiac critical care patients. Clin Pharmacokinet 47:449–462

    Article  CAS  PubMed  Google Scholar 

  44. Pettersen G, Mouksassi MS, Théoret Y, Labbe L, Faure C, Nguyen B, Litalien C (2009) Population pharmacokinetics of intravenous pantoprazole in paediatric intensive care patients. Br J Clin Pharmacol 67:216–227

    Article  CAS  PubMed  Google Scholar 

  45. Klotz U (2000) Pharmacokinetics considerations in the eradication of Helicobacter pylori. Clin Pharmacokinet 38:243–270

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Maria Jose Solana.

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Solana, M.J., López-Herce, J. Pharmacokinetics of intravenous omeprazole in critically ill paediatric patients. Eur J Clin Pharmacol 66, 323–330 (2010). https://doi.org/10.1007/s00228-009-0774-9

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