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  • Title: Plasma concentration of rabeprazole after 8-week administration in gastroesophageal reflux disease patients and intragastric pH elevation.
    Author: Yamano HO, Matsushita HO, Yanagiwara S.
    Journal: J Gastroenterol Hepatol; 2008 Apr; 23(4):534-40. PubMed ID: 17725594.
    Abstract:
    BACKGROUND AND AIM: The plasma concentration of rabeprazole in patients treated for gastroesophageal reflux disease (GERD) has not been reported, although the concentration in healthy volunteers has been reported previously. Here, CYP2C19 genotype effects of rabeprazole on the area under the plasma concentration-time curve (AUC) and the pH elevation were studied in GERD patients. METHODS: Rabeprazole 10 mg/day was administrated for 8 weeks. AUC of rabeprazole in 18 Helicobacter pylori-negative GERD subjects (five CYP2C19 homozygous extensive metabolizers [homEM], eight heterozygous extensive metabolizers [hetEM] and five poor metabolizers [PM]) were determined after the final medication. Intragastric pH was recorded for 24 h at baseline and after the final medication. RESULTS: The AUC in the PM group (957 ng x h/mL) was significantly higher than those of homEM (375 ng x h/mL) and hetEM (542 ng x h/mL) groups. Median 24-h pH curves, median 24-h pH values and 24-h and nocturnal pH > 4 and pH > 3 holding times did not significantly differ among these groups. Disappearance of erosive lesions was observed after the treatment in all subjects with grade A, B or C at baseline irrespective of CYP2C19 genotypes. CONCLUSION: The AUC of rabeprazole depended on the CYP2C19 genotypes in Japanese GERD patients; however, the intragastric pH elevation was independent of CYP2C19 genotypes, which is consistent with the CYP2C19 genotype-independent healing efficacy of erosive lesions by rabeprazole. The present low AUC values indicated that abnormal accumulative effects on AUC did not occur during the period of the 8-week administration of rabeprazole.
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