Rabeprazole 10 mg q.d.s. decreases 24‐h intragastric acidity significantly more than rabeprazole 20 mg b.d. or 40 mg o.m., overcoming CYP 2 C 19 genotype
Author(s) -
Sugimoto M.,
Shirai N.,
Nishino M.,
Kodaira C.,
Uotani T.,
Yamade M.,
Sahara S.,
Ichikawa H.,
Sugimoto K.,
Miyajima H.,
Furuta T.
Publication year - 2012
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12014
Subject(s) - rabeprazole , dosing , cyp2c19 , pharmacology , medicine , proton pump inhibitor , chemistry , omeprazole , gastroenterology , metabolism , cytochrome p450
Summary Background Standard dosing (i.e. once daily) of proton pump inhibitors ( PPI s) cannot inhibit acid secretion for a full 24 h. Better therapeutic regimens using PPI s are required to sustain potent acid inhibition for the full 24 h in all patients with acid‐related diseases. Aim To evaluate acid inhibitory effects by different dosing times of a PPI at the same daily dosage, in a study involving 70 rounds of pH monitoring. Methods Using pH monitoring, we evaluated the efficacy of different divided treatment regimens with the same total daily dose of rabeprazole (40 mg o.m., 15 rounds; 20 mg b.d., 20 rounds; 10 mg q.d.s., 35 rounds) on day 7 or 8 of PPI dosing. Results In the study of divided treatment, the median pH (when administered once, twice or four times to achieve a daily dose of 40 mg) was 4.8 (3.6–6.4), 5.7 (4.1–7.4), 6.6 (4.9–8.4), respectively. When comparing the median pHs at the same CYP2C19 genotype among different dosing times of rabeprazole, the median pH attained with 10 mg q.d.s. was significantly higher than that in 40 mg o.m. or 20 mg b.d. Increase in the frequency of dosing effectively increased pH [median percent time of pH > 4.0 with q.d.s. therapy: 95.5% (63.2–100.0%)], irrespective to CYP2C19 genotype. Conclusion Four times daily dosing with rabeprazole 10 mg achieved potent acid inhibition, including during the night‐time, suggesting its potential usefulness as a regimen for patients who are refractory to standard once daily PPI treatment.