0P-S5-1

INDICATIONS FOR PROTON PUMP INHIBITORS (PPI) IN PEDIATRICS

Vasundhara Tolia, M.D.

Children's Hospital of MI, USA

The PPIs are pyridyl-methyl-sulfinyl benzamidazoles that bind to the H⁺/K⁺ ATPase pump. They are converted to sulphenamides in presence of acid and are bound to exposed cysteine residues in the luminal domain of the pump. They produce a greater degree and duration of acid suppression than the H₂-receptor antagonists. Formal metanalyses have confirmed the superiority of PPIs in controlling intragastric acidity and intraesophageal acid exposure. The majority of peptic ulcers have been shown to be associated with Helicobacter pylori ( H.pylori) infection, and PPIs have been proven to improve the efficacy of co-administered antibiotics by improving their absorption and possibly also by a direct bactericidal effect. While most attention has been devoted to examining the efficacy of PPIs in adults, few studies have been conducted in the pediatric age group.

Although 5 PPIs are available for use in United States, pediatric data are available on omeprazole and lansoprazole only. Their major use has been for treatment of gastroesophageal reflux disease (GERD), erosive esophagitis and H. pylori infection. There have been no reported studies in the literature with the use of rabeprazole, pantoprazole or esomeprazole in children. Prospective studies to evaluate safety, efficacy, pharmacokinetics and pharmacodynamics of both omeprazole and lansoprazole have been conducted in children with reflux esophagitis. Descriptive studies of pH monitoring and endoscopy in the management of symptomatic infants and children before and after omeprazole have reported its efficacy and safety. Several reports of its use with different antibiotics in H. pylori gastritis with or without ulcer have been published as well. Experience with lansoprazole in children with esophagitis has also shown that it was well tolerated and effective in children. Its pharmacokinetic profile in adolescents was similar to that of healthy adults. However, children with predisposing factors to pathologic GERD, such as hiatal hernia, tracheo-esophageal fistula, or severe respiratory diseases do require higher than usual doses of PPIs. In summary, PPIs are being used frequently in the pediatric population. While the short term risk of complications appears to be minimal, chronic use of these drugs requires careful monitoring because of the potential consequences of prolonged inhibition of acid secretion.