The Pharmacokinetics of Pantoprazole Delayed Release Granules Administered by Three Different Methods in Healthy Subjects

Abstract

Purpose: A new oral delayed release granule formulation of pantoprazole was developed as an alternative for adult subjects who cannot swallow tablets. The primary objective of this study was to determine the bioequivalence of this new formulation administered by 3 different methods in healthy subjects. Methods: This was a randomized, open-label, 3-period, crossover, in-patient study in 25 healthy adult subjects aged 18 to 50 years. Each subject received a single 40 mg dose of pantoprazole after at least a 10 hour fast for each of the following administration methods separated by a washout period: 1) granules sprinkled over applesauce; 2) granules mixed with apple juice; 3) granules mixed with apple juice and administered through a nasogastric (NG) tube. Blood samples were collected up to 24 hours post dose and analyzed for pantoprazole levels by a validated LC/MS/MS method. Standard safety evaluations were performed. The PK parameters were estimated using non-compartmental methods. The 90% confidence limits for the test-to-reference geometric mean ratio were calculated for Cmax and AUC. Results: The mean Cmax, AUCT, and AUC values were similar for the 3 dosing methods. For Cmax, AUCT, and AUC, the 90% CI's for the ratio of the geometric means were within the bioequivalent limits of 80%–125%. Four subjects reported adverse events while on treatment including: headache, diarrhea, bronchitis, increased cough, epistaxis, and local reaction to the NG tube. There were no deaths, serious adverse events, or discontinuations. Conclusions: Pantoprazole granules administered with apple juice orally or through an NG tube, or with applesauce are bioequivalent. Pantoprazole granules were safe and well tolerated when administered by the above methods.