The World Health Organization has called childhood obesity one of the most serious public health challenges of the 21st century. The alarming childhood obesity epidemic brings with it increasing need for pediatricians to treat obesity-related diseases that traditionally have not had origins in childhood or adolescence, leading to a critical therapeutic information gap in pediatrics. Given that obese participants are often excluded from clinical trials during the drug development process, little to no information exists regarding the impact of obesity on drug disposition and action or the appropriate dosing of drugs in obese pediatric patients.
Obese children are more frequently diagnosed with gastroesophageal reflux disease (GERD) than children of normal weight. Proton pump inhibitors, such as pantoprazole, have become key components in the pharmacological management of GERD in pediatrics. In this multicenter, open-label, single-dose study of pantoprazole, the PTN examined the pharmacokinetics of the drug in obese children who required treatment with an acid-modifying agent. The data collected in this study were compared to existing pharmacokinetic data in non-obese subjects.
The study population comprised obese male and female children and adolescents, ranging in age from 6–17 years (inclusive) with the diagnosis of GERD. Approximately 40 participants were enrolled at four U.S. sites.
The study found that the PK of pantoprazole in children is affected by obesity, with higher exposures and slower drug clearance observed in obese children and adolescents relative to their nonobese, age-matched peers. Dosing based on lean body weight led to pantoprazole PK similar to nonobese peers.
- A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents Pediatric Drugs • October 2018. Shakhnovich V, Brian Smith P, Guptill JT, James LP, Collier DN, Wu H, Livingston CE, Zhao J, Kearns GL, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act–Pediatric Trials Network. Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk for ...
- Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures The Journal of Pediatrics • February 2018. Shakhnovich V, Smith PB, Guptill JT, James LP, Collier DN, Wu H, Livingston CE, Zhao J, Kearns GL; Best Pharmaceuticals for Children Act – Pediatric Trials Network. To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient population ...
Completed; clinical study report submitted to FDA
P. Brian Smith, MD, MPH, MHS
Duke Health, Durham, NC
Valentina Shakhnovich, MD
Children’s Mercy Hospital
Kansas City, MO
- Dr. Shakhnovich offers guidelines for prescribing GERD medications to obese kids When treating gastroesophageal reflux disease (GERD) in obese kids, the common practice of dosing stomach acid blockers based on children’s weight could actually cause more harm than good, said Dr. Valentina Shakhnovich, investigator for the Pediatric Trials Network (PTN) and Associate Program Director for the Gastroenterology Fellowship Research Program at Children’s Mercy Hospitals in Kansas ...
- PTN Pantoprazole Study Closes Enrollment Congratulations to the PTN Pantoprazole Study Team for closing enrollment with 41 subjects. The study goal was to enroll 40 subjects in two age groups. The dedicated team worked hard to keep the study on track and accomplish this goal. The Pantoprazole Study will evaluate the pharmacokinetics of pantoprazole in obese children and adolescents with gastroesophageal reflux ...
- The PTN pantoprazole study enrolls its first patient The PTN study of the effect of obesity on the pharmacokinetics of pantoprazole in children and adolescents has enrolled its first patient. The study team at Arkansas Children’s Hospital (PI Laura James, MD, SC Lee Howard, RN) did the honors. Obese children are more frequently diagnosed with gastroesophageal reflux disease (GERD) than children of normal weight. ...