About this pathway
Background
Lidocaine is widely used as a local anesthetic, including in dental practice [Article:30117019]. It is also used intravenously as an antiarrhythmic drug (link PD) [Article:18027986][Article:14749694].
Metabolism
Metabolism of lidocaine occurs primary in the liver with around 80% of dose excreted as metabolites [Article:12019189][Article:3443650]. The major route is deethylation to monoethylglycinexylidide (MEGX) and further deethylation to glycinexylidide and hydrolysis to 2,6-xylidine [Article:12019189]. CYP1A2 and CYP3A4 are the major enzymes involved in lidocaine deethylation [Article:10901707][Article:14749694]. An alternative route for formation of 2,6-xylidine can occur via the CES1 enzyme [Article:12019189]. In humans 3-hydroxylidocaine is a very minor product, the major excreted metabolite is 4-hydroxyxylidine [Article:12019189].
MEGX exhibits pharmacological properties comparable to those of lidocaine but with a less potency (about 80–90% of its antiarrhythmic and anticonvulsant potencies) [Article:30117019].
Toxicity
Methemoglobinemia is a rare side effect cautioned in the drug label for lidocaine. Individuals with G6PD deficiencies are generally at greater risk for drug induced methemoglobinemia. The metabolite 2,6-xylidine may be further metabolized to 4-hydroxyxylidine by CYP2E1 which is able to induce formation of methemoglobin in vitro [Article:23530020].
Reactions & interactions (19)
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Biochemical Reaction
2,6-dimethylxylidine → 4-hydroxyxylidine
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Biochemical Reaction
glycinexylidide → 2,6-dimethylxylidine
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Biochemical Reaction
monoethylglycinexylidide → glycinexylidide
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Biochemical Reaction
lidocaine → 2,6-dimethylxylidine
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Biochemical Reaction
lidocaine → 3-hydroxylidocaine
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Biochemical Reaction
2,6-dimethylxylidine → 2,6-dimethylphenylhydroxylamine
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Biochemical Reaction
lidocaine → monoethylglycinexylidide
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Biochemical Reaction
monoethylglycinexylidide → 2,6-dimethylxylidine
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Catalysis
CYP2E1 → Biochemical Reaction
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Catalysis
CES1 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Catalysis
CYP2B6 → Biochemical Reaction
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Catalysis
CYP2A6 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP2D6 → Biochemical Reaction
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Catalysis
CYP1A2 → Biochemical Reaction
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Catalysis
CYP3A4 → Biochemical Reaction
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Leads To
4-hydroxyxylidine → Methemoglobinemia
Edit history (1)
- 2019-04-01 Create