PMID- 15903128
OWN - NLM
STAT- MEDLINE
DCOM- 20050602
LR  - 20190513
IS  - 0009-9236 (Print)
IS  - 0009-9236 (Linking)
VI  - 77
IP  - 4
DP  - 2005 Apr
TI  - Comparison of an increased dosage regimen of rabeprazole versus a concomitant 
      dosage regimen of famotidine with rabeprazole for nocturnal gastric acid 
      inhibition in relation to cytochrome P450 2C19 genotypes.
PG  - 302-11
AB  - BACKGROUND AND OBJECTIVE: A concomitant dosage regimen of a histamine 2 receptor 
      antagonist with a proton pump inhibitor (PPI) effectively decreases the incidence 
      of nocturnal acid breakthrough, which is one of the problems encountered when 
      acid-related diseases are treated with a PPI alone. We compared the effectiveness 
      of an increased dosage regimen of rabeprazole with that of a concomitant dosage 
      regimen of rabeprazole with famotidine, relative to cytochrome P450 (CYP) 2C19 
      genotype status, on nocturnal acid inhibition. METHODS: Fifteen Helicobacter 
      pylori-negative volunteers, consisting of 5 homozygous extensive metabolizers 
      (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took 20 mg 
      rabeprazole, 40 mg rabeprazole, and 20 mg rabeprazole plus 20 mg famotidine at 
      bedtime (at 10 PM) for 8 days. The subjects then underwent 24-hour intragastric 
      pH monitoring on day 8. RESULTS: For the 20-mg rabeprazole, 40-mg rabeprazole, 
      and concomitant dosage regimens, the median percent times and ranges when 
      nocturnal intragastric pH values were lower than 4.0 were 78.8% (47.5%-98.0%), 
      45.3% (29.0%-52.2%), and 15.5% (0.0%-40.8%), respectively, for homozygous EMs; 
      51.0% (7.0%-91.6%), 41.3% (33.0%-59.0%), and 18.5% (8.4%-31.9%), respectively, 
      for heterozygous EMs; and 4.5% (2.0%-31.2%), 9.5% (0.0%-31.1%), and 9.3% 
      (0.0%-14.7%), respectively, for PMs. Although significant differences in acid 
      inhibition between the different CYP2C19 genotypes were observed when rabeprazole 
      alone was given (P = .016 for 20 mg rabeprazole and P = .023 for 40 mg 
      rabeprazole), such differences were not observed when famotidine was 
      concomitantly given (P = .206). CONCLUSIONS: The combination regimen of 
      famotidine plus rabeprazole is more effective for nocturnal acid inhibition in 
      homozygous and heterozygous EMs than the increased dosage regimen of rabeprazole. 
      This concomitant therapy could be a rescue regimen for patients with nocturnal 
      acid breakthrough refractory to a standard PPI therapy who are likely to be 
      CYP2C19 EMs.
FAU - Sugimoto, Mitsushige
AU  - Sugimoto M
AD  - First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, 
      Japan. mitsu@hama-med.ac.jp
FAU - Furuta, Takahisa
AU  - Furuta T
FAU - Shirai, Naohito
AU  - Shirai N
FAU - Nakamura, Akiko
AU  - Nakamura A
FAU - Kajimura, Masayoshi
AU  - Kajimura M
FAU - Hishida, Akira
AU  - Hishida A
FAU - Ohashi, Kyoichi
AU  - Ohashi K
FAU - Ishizaki, Takashi
AU  - Ishizaki T
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Benzimidazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histamine H2 Antagonists)
RN  - 32828355LL (Rabeprazole)
RN  - 5QZO15J2Z8 (Famotidine)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP2C19 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.3.14 (Proton-Translocating ATPases)
RN  - KG60484QX9 (Omeprazole)
SB  - IM
MH  - 2-Pyridinylmethylsulfinylbenzimidazoles
MH  - Adenosine Triphosphatases/antagonists & inhibitors
MH  - Adult
MH  - Aryl Hydrocarbon Hydroxylases/genetics
MH  - Benzimidazoles/administration & dosage/*pharmacology
MH  - Circadian Rhythm
MH  - Cytochrome P-450 CYP2C19
MH  - Drug Synergism
MH  - Drug Therapy, Combination
MH  - Enzyme Inhibitors/administration & dosage/*pharmacology
MH  - Famotidine/administration & dosage/*pharmacology
MH  - Female
MH  - Gastric Acid/*metabolism
MH  - Genotype
MH  - Histamine H2 Antagonists/administration & dosage/*pharmacology
MH  - Humans
MH  - Male
MH  - Mixed Function Oxygenases/genetics
MH  - Omeprazole/administration & dosage/*analogs & derivatives/*pharmacology
MH  - Polymorphism, Genetic
MH  - Proton-Translocating ATPases/antagonists & inhibitors
MH  - Rabeprazole
EDAT- 2005/05/21 09:00
MHDA- 2005/06/03 09:00
CRDT- 2005/05/21 09:00
PHST- 2005/05/21 09:00 [pubmed]
PHST- 2005/06/03 09:00 [medline]
PHST- 2005/05/21 09:00 [entrez]
AID - 10.1016/j.clpt.2004.10.010 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2005 Apr;77(4):302-11. doi: 10.1016/j.clpt.2004.10.010.