Abstract
OBJECTIVES: Vonoprazan, a potassium-competitive acid blocker, provides more rapid, potent, and durable elevations in gastric pH than proton pump inhibitors in adults and may be a treatment option for adolescents and children with gastroesophageal reflux disease (GERD). The pharmacokinetics and safety of vonoprazan in pediatric subjects (6-17 years) with symptomatic GERD were evaluated in two clinical studies.
METHODS: Forty-two subjects were randomized to vonoprazan 10 or 20 mg once daily for 14 days. Plasma vonoprazan concentrations were analyzed employing a two-compartment population pharmacokinetic model developed using adult data. Individual estimates of maximum concentration at steady state (Cmax,SS) and area under the drug concentration-time curve during the dosing interval τ at steady state (AUCτ,SS) were calculated. Individual apparent oral clearance (CL/F) and central volume of distribution (Vc/F) were calculated from the model-based estimates. The effect on GERD symptoms and their severity was qualitatively assessed.
RESULTS: Model-based analyses showed that exposures (AUCτ,ss) of vonoprazan in pediatric subjects (6-17 years) were nearly identical to adult exposures. Model-based exposure estimates from pediatric subjects were also nearly identical to noncompartmental exposure estimates from adults in other studies for both vonoprazan doses. Subjects reported improvement in GERD symptoms, regardless of vonoprazan dosage. There were six treatment-emergent adverse events, one of which was related to the study drug; none were serious, nor resulted in treatment discontinuation.
CONCLUSIONS: Exposures of vonoprazan in adolescents and children were nearly identical to exposures observed in adults, confirming the appropriateness of vonoprazan 10 and 20 mg doses in a pediatric population.