About this pathway
Background
Proton pump inhibitors (PPIs) are a class of drugs that block the acid secretion from parietal cells in the stomach, thereby providing relief from acid-related disorders (see Proton Pump Inhibitor Pathway, Pharmacodynamics ). Rabeprazole is a second generation PPI.
Although PPIs are active in the stomach, they are primarily metabolized in the liver by CPY2C19 and CYP3A4. CYP2C19 genotypes have been linked to PPI exposure, with lower exposure associated with treatment failure. There is a CPIC Dosing Guideline for omeprazole, lansoprazole, pantoprazole based on CYP2C19 genotypes but the evidence for rabeprazole was considered weak and therefore has no recommendations given [Article:32770672].
Metabolism
The metabolism of rabeprazole is less dependent on CYP2C19 than other PPIs [Articles:32770672, 28294690]. Rabeprazole is converted to rabeprazole thioether via non-enzymatic reduction [Articles:28294690, 31846760, 23512128]. This can be reversed by CYP3A4 at a much slower rate. Rabeprazole thioether is converted to desmethyl rabeprazole thioether by CYP2C19 [Articles:28294690, 23512128]. The desmethyl rabeprazole thioether metabolite can also be formed by another route: rabeprazole is demethylated by CYP2C19 and then forms desmethyl rabeprazole thioether by non-enzymatic methods or it may involve CYP2D6 [Articles:28294690, 23512128].
Reactions & interactions (11)
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Biochemical Reaction
desmethyl rabeprazole → desmethyl rabeprazole thioether
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Biochemical Reaction
rabeprazole → rabeprazole sulfone
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Biochemical Reaction
rabeprazole thioether → desmethyl rabeprazole thioether
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Biochemical Reaction
rabeprazole → desmethyl rabeprazole
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Biochemical Reaction
rabeprazole → rabeprazole thioether
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Biochemical Reaction
rabeprazole thioether → rabeprazole
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Catalysis
CYP2D6 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP2C19 → Biochemical Reaction
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Catalysis
CYP2C19 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
Edit history (1)
- 2020-12-09 Create