The use of proton pump inhibitors in children: a comprehensive review

Proton pump inhibitors (PPIs) belong to a group of chemically related compounds whose primary function is the inhibition of acid production in the final common metabolic pathway of gastric parietal cells. PPIs are highly selective and effective in their action and have few short- or long-term adverse effects. These pharmacologic features have made the development of PPIs the most significant advancement in the management of acid peptic related disorders in the last two decades. There are numerous published adult studies that describe the pharmacology, efficacy and safety of these anti-secretory agents; however, in the pediatric population, there are very few comparable studies, particularly multicenter studies with significant patient enrollment. In preparing this article, our aim was to perform a comprehensive review of the literature on the clinical pharmacology and use of PPIs in the pediatric population, and to briefly review some recent articles. Relevant literature was identified by performing MEDLINE/Pubmed searches from January 1990 to December 2001. Combinations of the following search terms were use to analyze these databases: proton pump inhibitor, children, pediatrics, gastroesophageal reflux disease (GERD), esophagitis, intestinal metaplasia, Helicobacter pylori, omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole, and safety. Abstracts from the 14th annual conference of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) 2001, and the Disease and Digestive Week 2001, were also included in the review. All pediatric studies reviewed were limited to either omeprazole or lansoprazole. The dosage range used for the management of GERD and related disorders with lansoprazole was 0.73-1.66 mg/kg/day (maximum 30 mg/day). The dosage range for GERD management using omeprazole was 0.3-3.5 mg/kg (maximum 80 mg/day). The dosage range for omeprazole used for H. pylori was 0.5-1.5 mg/kg/day, with a maximum dosage of 40 mg/day, and lansoprazole-containing regimens for H. pylori eradication used dosages ranging from 0.6-1.2 mg/kg/day, with a maximum dosage of 30 mg/day. Few severe adverse events were reported with the use of either drug. Eradication rates for H. pylori were 56-87% for lansoprazole-based triple therapy, and 75-94% for omeprazole-based eradication regimens. To date, there are no published controlled trials of sufficient power comparing the efficacy of the five commercially available PPIs in children, for a variety of acid peptic diseases. Studies suggest that PPIs are highly effective for the management of GERD and related disorders, and are a critically needed component of triple therapy to eradicate H. pylori. PPIs have a very good tolerability profile in adults and children, but long-term tolerability studies are needed, particularly in the pediatric population. Multicenter studies are critically needed to evaluate the second-generation PPIs, to compare PPI efficacy to each other, and to assess the importance of developmental and genetic pharmacology of these drugs in children with acid-peptic disease.