Pharmacokinetics of a New Immediate-release Compound Omeprazole Capsule and its Comparison with the Enteric-coated Formulation under Fasting and Fed Conditions

Abstract

The present study was conducted to describe the pharmacokinetic profile of immediate-release compound omeprazole capsule and compare it with the enteric-coated formulation under fasting and fed condition.This study was designed to phase I, open-label, randomized, 3-part clinical trial. 12 subjects in part one received single doses (20 mg and 40 mg) and repeated doses (20 mg). Different 30 subjects in part 2 (fasting condition) and part 3 (fed condition) received either compound omeprazole capsule (40 mg) or delayed-release omeprazole (40 mg) separated by 7 days.Compound omeprazole capsule showed dose non-proportionality in the range from 20 mg to 40 mg. The AUC0-t of 20 mg omeprazole is 78% higher after repeated doses. The C max was higher and T max was lower for compound omeprazole capsule than delayed-release omeprazole. 90% CIs for AUC0-t of the 2 periods (test/reference) under fasting and fed conditions were 106.3% (102.2%~109.2%) and 104.1% (93.4%~109.6%), respectively. Presence of food reduced the rate (C max) and extent (AUC0-t) of systemic exposure of the test and reference formulations from 1 462 to 777 ng · mL-1, 1 055 to 602 ng · mL-1, 2 597 to 1 852 ng · h · mL-1 and 2 454 to 1 873 ng · h · mL-1, respectively.Exposed dose of omeprazole in subjects with compound omeprazole capsule was time- and dose-dependent. Compared with delayed-release omeprazole, compound omeprazole capsule had rapid but similar degree of absorption of omeprazole.

In vitro dissolution of proton-pump inhibitor products intended for paediatric and geriatric use in physiological bicarbonate buffer

“…Similar results were shown in another study conducted in healthy volunteers in both fasted and fed conditions (Z. Liu et al, 2013). This is better reflected by the in vitro drug release results in pH 6.8 mHanks buffer than phosphate buffer, as the former reveals the difference in drug release profiles between the tested PPI products as well as the variation in drug release in the six dissolution test repetitions of the same product (as shown by the higher standard deviation in tlag, t80 and release rate).…”

“…The reported in vivo tmax values for omeprazole products range from 1.9 to 4.0 hours (K. Boussery et al, 2011;S. Karim et al, 2014;Z. Liu et al, 2013) and the in vitro t80 values are 0.9-1.3 and 1.2-2.2 hours in pH 6.8 phosphate buffer and mHanks buffer respectively.…”

Effect of food on the pharmacokinetics of omeprazole, pantoprazole and rabeprazole

“…In our opinion, a low-fat breakfast would also influence PPI absorption, however, the effect might be less noticeable and maybe not clinically relevant. In this regard, the presence of food has been reported to reduce the C max and AUC of omeprazole [21] and esomeprazole [13]. Thomson et al found that the evening meal reduced the tenatoprazole AUC compared with evening administration of the drug under fasting conditions [14].…”

Effect of Food and Dosing Regimen on Safety and Efficacy of Proton Pump Inhibitors Therapy—A Literature Review

“…When capsules or powder for oral suspension were administered 1 h after a meal, both AUC and C max decreased by 24% and 63%, respectively [32]. Liu et al [34] performed a randomized, open-label study involving 30 healthy subjects who were given a single 40 mg IR omeprazole capsule (containing sodium bicarbonate) while fasting or with a standard meal. The meal consisted of two pieces of bread, two sausages, two eggs, 100 g of salad, and 250 mL of milk.…”

“…After 7 days of each dosing regimen, significant changes were observed in the pharmacokinetic profiles of both DR products: not only C max decreased (by 58% and 63%), but AUC 0-12 also decreased (by 35% and 38%). Additionally, Liu et al [34] reported a negative effect of food on the AUC of DR omeprazole capsules.…”