Influence of the Meal and Genotype of CYP2C19 on the Pharmacokinetics of Proton Pump Inhibitors in Healthy Japanese Subjects

Abstract

Objectives: To evaluate the influence of meals on the pharmacokinetics of omeprazole and rabeprazole and to investigate these PPIs with reference to CYP2C19 genotypes in healthy Japanese men. Methods: This was a randomized, open label, four-way crossover study. Twelve healthy Japanese male volunteers received a single oral dose of either 20 mg omeprazole or 10 mg rabeprazole, in the fasted state and after a standardized breakfast. Results: Between the administration of omeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC, Tmax, and half-life. Between the administration of rabeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC and half-life, whereas the Tmax of rabeprazole after breakfast was significantly delayed (2.8 ± 1.0 vs 5.3 ± 1.8 h, respectively; p = 0.006). PMs demonstrated the highest Cmax and AUC after drug intake under the fasting state and after breakfast, and homo EMs showed a significantly delayed Tmax. Conclusion: When a single dose of either PPI was administered, the pharmacokinetics of omeprazole was not affected by the meal, whereas the Tmax of rabeprazole after the meal was significantly delayed.

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

“…Except for the delay of t max (2.2 h for (1) vs. 3.5 h for (3)), no significant changes were observed in AUC and C max values between all the investigated regimens. Shinkai et al [42] reported the nonsignificant effect of food on 20 mg omeprazole pharmacokinetic parameters (namely C max , AUC 0-t , t max , and t1 ⁄2 ); however, in this study, drug formulation was not mentioned.…”

“…To assess the effect of a meal on the pharmacokinetic parameters of rabeprazole tablets, Shinkai et al [42] performed a randomized, open-label study in 12 healthy volunteers. Each of the participants ingested a single 10 mg dose of rabeprazole either while fasting or after breakfast that contained on average 712 kcal.…”

“…We are convinced that knowledge on this subject is vital to professionally educate patients with the aim to improve their compliance and increase the effectiveness of PPI therapy. -should be taken 60 min before a meal [40] -should be placed on the tongue to disintegrate and swallowed, with or without water [40] DR capsules ↓ AUC (by 35-38%) [34], ↓ C max (by 24-40% and 58-63%, depending on the study) [36,38], ↑ t max (by 2 h) [36] -should be taken 60 min before a meal [33] -should be swallowed whole or with content mixed with 15 mL of applesauce [33] DR granules for oral suspension no studies found -should be taken 60 min before a meal [33] -should be mixed with 5-15 mL of water [33] DR tablets no significant changes in AUC and C max , ↑ t max (by 1.3 h) [41] -can be taken with or without food [41] -should be swallowed whole with water [41] -can be taken with or without food [56,59] -should be swallowed whole with water [56,59] -preferably should be administered in the morning [61] DR granules for oral suspension ↓ AUC (by 29%), ↓ C max (by 51%), ↑ t max (by 2 h) [56] -should be taken 30 min before a meal [56] -content should be sprinkled into 5 mL of applesauce/apple juice [56,62] -do not mix with water or other liquids or food [56] Rabeprazole DR capsules ↓ AUC (by 27%), ↓ C max (by 55%), ↑ t max (by 2 h) [65] -should be taken 30 min before a meal [63] -content should be sprinkled onto a small amount of applesauce/apple juice/yoghurt/fruit or vegetable-based baby food/infant formula/pediatric electrolyte solution [63,65] -can be administered both in the morning or in the evening [67] -evening intake can be beneficial for patients with nocturnal acid breakthrough or nocturnal reflux [66] DR tablets no significant changes in AUC and C max , ↑ t max (by 2.5 h) [42] no significant changes in median intragastric pH [23,24] -can be taken with or with...…”

Exploring Differences in Pharmacometrics of Rabeprazole between Genders via Population Pharmacokinetic–Pharmacodynamic Modeling

“…Nevertheless, it has been suggested that careful judgment and monitoring are needed for administration in patients with severe liver disease [9]. Some past reports [10,11] have suggested that the pharmacokinetic effects of rabeprazole from food may not be significant. According to a past report [11], no clinically relevant differences were detected in the area under the curve for the plasma concentration-time profiles (AUC), maximum plasma concentration (C max ), and half-life (T 1/2 ) of rabeprazole between fasted and fed conditions.…”

Esomeprazole Inhibits the Pentagastrin-Stimulated Secretion of Gastric Acid in Healthy Japanese Volunteers

“…pylori status and CYP2C19 polymorphism genotyping H. pylori infection status was determined by measuring titers of anti-H. pylori IgG in the serum samples using an EIA kit (E Plate "Eiken" H. pylori-antibody II; Eiken Chemical Co. Ltd., Tokyo, Japan). A genotype of CYP2C19 gene, which encodes a hepatic enzyme involved in metabolism of esomeprazole, was determined using fluorescence correlation spectroscopy (Shinkai et al 2013). Genomic DNA was extracted from venous white blood cells, and used as a template for polymerase chain reaction (PCR) to specifically amplify fluorescent-labeled DNA fragments with wild-type (wt) or mutant sequence.…”