European Journal of Clinical Pharmacology

, Volume 70, Issue 9, pp 1073–1078 | Cite as

Comparison of acid inhibition with standard dosages of proton pump inhibitors in relation to CYP2C19 genotype in Japanese

  • Mitsushige SugimotoEmail author
  • Naohito Shirai
  • Masafumi Nishino
  • Chise Kodaira
  • Takahiro Uotani
  • Shu Sahara
  • Hitomi Ichikawa
  • Takuma Kagami
  • Ken Sugimoto
  • Takahisa Furuta



The aim of therapeutic regimens using proton pump inhibitors (PPIs) in patients with acid-related diseases is to potently inhibit acid secretion for the full 24 h. However, optimum treatment is still unclear because the pharmacodynamics of PPIs differ among CYP2C19 genotypes and most of the previous studies have had loss of sample power.


Using pH monitoring, we compared acid inhibition at standard dosage of omeprazole (20 mg, 50 times), lansoprazole (30 mg, 68 times), and rabeprazole (10 mg, 65 times) in Helicobacter pylori-negative healthy young Japanese volunteers.


Median pH with rabeprazole was 5.4 (3.3–7.5), which was significantly greater than with either omeprazole [4.4 (2.1–7.3)] or lansoprazole [4.8 (3.5–6.4)] (both P < 0.05). Median 24-h pH differed among the different CYP2C19 genotypes in all three PPIs. In CYP2C19 extensive metabolizers (EMs), the genotype that is refractory to PPI treatment, median pH with omeprazole, lansoprazole, and rabeprazole was 3.8 (2.1–4.4), 4.5 (3.5–5.3) and 4.8 (3.3–7.5), respectively.


Treatment with the selected PPIs at their standard dosages had difficulty maintaining acid inhibition for a full 24 h, especially in CYP2C19 EM. However, rabeprazole has the merit of less influence of CYP2C19 genotype compared with the other PPIs.


CYP2C19 Intragastric pH Proton pump inhibitor Rabeprazole 



S-mephenytoin 4′-hydroxylase


Extensive metabolizer


Intermediate metabolizer


Proton pump inhibitor


Poor metabolizer



This study was supported by a grant-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (22790640 and 24590912).

Conflicts of interest

None of the authors has any conflict of interest related to this study.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Mitsushige Sugimoto
    • 1
    Email author
  • Naohito Shirai
    • 3
  • Masafumi Nishino
    • 3
  • Chise Kodaira
    • 1
  • Takahiro Uotani
    • 1
  • Shu Sahara
    • 1
  • Hitomi Ichikawa
    • 1
  • Takuma Kagami
    • 1
  • Ken Sugimoto
    • 1
  • Takahisa Furuta
    • 2
  1. 1.First Department of MedicineHamamatsu University School of MedicineHamamatsuJapan
  2. 2.Center for Clinical ResearchHamamatsu University School of MedicineHamamatsuJapan
  3. 3.Department of GastroenterologyEnshu General HospitalShizuokaJapan

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