As the pediatric obesity epidemic continues to rise, obesity-associated pathologic conditions, such as type II diabetes, hypertension and gastroesophageal reflux disease (GERD), become more prevalent, which, in turn, creates a need for a better understanding of the impact of obesity on drug disposition and response in pediatric patients with obesity. The following proposal is designed to address the hypothesis that obesity per se has significant effects on the pharmacokinetics of CYP2C19 substrates in children and adolescents. Pantoprazole, a proton pump inhibitor (PPI) frequently used in the treatment of GERD and related conditions, is ideally suited for such a study, given the predominant role of CYP2C19(Cytochrome P450 subtype 2C19) in its metabolism and its favorable safety and efficacy profile in pediatric medicine. The study of obesity on the activity of CYP2C19 is relevant, as it has not been previously studied in pediatrics and the enzyme catalyzes the biotransformation of over 20 drugs frequently used in pediatrics (eg., PPIs, selective serotonin re-uptake inhibitors). Moreover, knowledge of the CYP2C19 genotype and phenotype can be used to individualize drug treatment, making treatment safer and more effective for children. The primary objective of the proposed investigation is to evaluate the effect of obesity on the pharmacokinetics of pantoprazole in children and adolescents. The secondary objective is to assess the utility of the [13C]-pantoprazole breath test, a novel, non-invasive, in-vivo technique, as a surrogate biomarker of CYP2C19 activity in pediatric patients. In addition, the impact of non-genetic variables, such as resting energy expenditure (REE), on CYP2C19 activity will be investigated. The proposed research objectives will be achieved by administration of a single dose of oral [13C]-pantoprazole, a safe and stable non-radioactive isotope, to 100 patients (both male and female), including 50 obese (as defined by BMI >95th percentile) and 50 non-obese patients, between the ages of 6-17 years. Breath samples will be collected before, and for 8 hours after, [13C]-pantoprazole administration to quantify 13CO2(Carbon 13 dioxide)/12CO2(Carbon 12 dioxide) by infrared spectrometry. Simultaneously, repeated blood sampling will be used to measure pantoprazole, and its primary CYP2C19 catalyzed metabolite. Pantoprazole disposition will then be characterized from both breath sample and plasma level data and examined in association with important covariates (e.g., age, hip:waist ratio, BMI, REE, parent drug:metabolite ratio and CYP2C19 genotype) to test the experimental hypothesis. Data will be collected and analyzed by a team of highly experienced investigators representing the fields of gastroenterology, pediatric clinical pharmacology and the evolving field of obesity medicine.