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 ). Different drugs within the class are prescribed for different patient groups with esomeprazole and lansoprazole for pediatric erosive esophagitis and esomeprazole for infant and pediatric GERD [Article:23512128]. 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, dexlansoprazole, lansoprazole, pantoprazole based on CYP2C19 genotypes.
Metabolism
Lansoprazole is a racemic mixture of R-lansoprazole and S-lansoprazole [Article:11829200]. The R enantiomer is also marketed separately as dexlansoprazole [Article:20371754]. Lansoprazole is primarily metabolized via CYP2C19 to 5-hydroxylansoprazole [Articles:19652384, 23512128, 31846760]. It can also be metabolized by CYP3A4 to the sulfone and sulfide forms [Articles:19652384, 23512128, 31846760]. The sulfone can be further metabolized by CYP2C19 to 5-hydroxylansoprazole, which can also be formed by CYP3A4 acting on 5-hydroxylansoprazole [Articles:23512128, 31846760]. The stereoisomers do show some differences in pathway routes with the R-lansoprazole favoring the route via CYP3A4 to the sulfone and S-lansoprazole via CYP2C19 [Article:12152007].
Transport
Lansoprazole is a substrate for ABCB1 and there is preliminary evidence for ABCB1 variants influence on lansoprazole pharmacokinetics [Articles:11770010, 17190370]
Reactions & interactions (16)
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Biochemical Reaction
lansoprazole → lansoprazole sulfone
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Biochemical Reaction
dexlansoprazole → lansoprazole sulfone
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Biochemical Reaction
lansoprazole → 5-hydroxylansoprazole
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Biochemical Reaction
dexlansoprazole → 5-hydroxylansoprazole
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Biochemical Reaction
lansoprazole sulfone → 5-hydroxylansoprazole sulfone
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Biochemical Reaction
5-hydroxylansoprazole → 5-hydroxylansoprazole sulfone
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Biochemical Reaction
lansoprazole → lansoprazole sulfide
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Catalysis
ABCB1 → Transport
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Catalysis
CYP3A4 → 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
CYP2C19 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Transport
lansoprazole → lansoprazole
Edit history (2)
- 2021-04-26 Create
- 2021-04-28 Update Added text