Performance Differences between Zegerid® and PrilosecTM Dosage Forms: A Comparative Bioavailability Study

Purpose: The primary objective of this trial was to test for bioequivalence between Zegerid® OTC Capsules 20 mg and Prilosec OTCTM Delayed-Release Tablets 20 mg. Methods: This study was an open-label, randomized, two-period crossover trial, with each subject receiving single doses of Zegerid® CAP and Prilosec OTCTM Tablets. One-hundred thirty-four (134) healthy male and female subjects between the ages of 18-45 successfully completed the study. Data from 134 subjects who completed the study were included in the pharmacokinetic and statistical analyses. Data were analyzed by noncompartmental methods in WinNonlin Enterprise Edition (Version 4.0, Pharsight Corporation). Post-hoc analyses were performed in S-Plus (TIBCO Spotfire S+®8.1 for Windows). Results: Zegerid® administration resulted in higher maximal plasma levels and systemic exposure than Prilosec. The point estimate for the Cmax, AUCt, and AUCinf ratios (Zegerid®/PrilosecTM) were 220%, 117%, and 116%, respectively. The upper confidence limits for the Cmax and AUCt ratios exceeded the FDA threshold value of 125% for bioequivalence. Therefore, Zegerid® and PrilosecTM were not bioequivalent in this study. Investigation into the cause for the disparate results between Zegerid® and PrilosecTM resulted in identification of a sub-population of subjects (n=32) with delayed absorption following PrilosecTM administration (i.e., Tmax >4 hr). When these subjects were excluded from analysis of AUCt and AUCinf ratios, the two dosage forms performance was nearly identical with a point estimate ratio of 103% for both AUCt and AUCinf (n=102 subjects). To calculate the exposure ratio in the PrilosecTM delayed Tmax group, Zegerid® AUCt values were used as reference values resulting in a point estimate of 56.6% and a 90% CI of 51.5-62.2%. Conclusion: Zegerid® was not shown to be bioequivalent to PrilosecTM in this study. Subsequent investigation identified a bimodal distribution of Tmax values following PrilosecTM administration. Low exposure values in a sub-population of 32 subjects with Tmax >4 hr were identified as the main causative factor for not achieving bioequivalence. These 32 subjects, on average, only received ˜57% of the expected exposure following Prilosec administration. Failure of the PrilosecTM dosage form in 24% of the subjects (32/134) increased the point estimate and expanded the confidence intervals for the AUC ratios (Zegerid®/Prilosec) TM. Cmax differences were expected between dosage forms, due to Zegerid® being an immediate release product and PrilosecTM being a delayed release product. Differential bioavailability of the two dosage forms in a subset of subjects may in part explain the observed PK profile differences between these two products in this study. Disclosure - Zegerid is distributed by MSD Consumer Care, Inc. Prilosec is distributed by P&G. Dr. Kearbey - Employee: MSD Consumer Care, Inc. Dr. McGraw - Employee: MSD Consumer Care, Inc. Dr. O'Mullane - Employee: MSD Consumer Care, Inc. Dr. Miller - Employee: MSD Consumer Care, Inc. Dr. Mishra - Employee: MSD Consumer Care, Inc.