About this pathway
Background
Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) indicated for rheumatoid arthritis and osteoarthritis and as a topical solution for ophthalmic conditions.
The pharmacodynamics of flurbiprofen has similarities with other NSAIDs such as that depicted for ibuprofen at Ibuprofen Pathway, Pharmacodynamics. However, flurbiprofen is highly selective for PTGS1 (Cox1) over PTGS2 whereas ibuprofen is essentially nonselective [Article:9626023].
The CPIC Dosing Guideline for celecoxib, flurbiprofen, ibuprofen and lornoxicam recommends initiating therapy with 25-50% of the lowest recommended starting dose for CYP2C9 poor metabolizers and initiating therapy with lowest recommended starting dose for CYP2C9 intermediate metabolizers with activity score of 1. Dosage reduction for CYP2C9 poor metabolizers or *3 carriers is also discussed on the FDA label and in the FDA Table of Pharmacogenetic Associations.
Metabolism
Flurbiprofen is given as a racemic mixture but only the S enantiomer is considered active [Article:7763308]. Flurbiprofen is metabolized to 4’hydroxy, dihydroxy and hydroxy methoxy metabolites [Articles:7736686, 7763308].
Initial in vitro experiments with human liver microsomes and CYP-targeted inhibitors showed the major metabolizing enzyme for flurbiprofen was CYP2C9 and suggested potential minor involvement of CYP1A2 [Article:7763308]. Further studies with specific expressed proteins showed the only major enzyme catalyzing generation of 4’-hydroxy flurbiprofen is CYP2C9 [Article:8937439].
Reactions & interactions (8)
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Biochemical Reaction
flurbiprofen → flurbiprofen glucuronide
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Biochemical Reaction
4'-hydroxyflurbiprofen → 3',4'-dihydroxyflurbiprofen
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Biochemical Reaction
flurbiprofen → 4'-hydroxyflurbiprofen
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Biochemical Reaction
flurbiprofen → 3',4'-dihydroxyflurbiprofen
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Biochemical Reaction
3',4'-dihydroxyflurbiprofen → 3'-hydroxy-4'-methoxyflurbiprofen
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Catalysis
UGT1A9 → Biochemical Reaction
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Catalysis
UGT2B7 → Biochemical Reaction
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Catalysis
CYP2C9 → Biochemical Reaction
Edit history (2)
- 2021-06-08 Create
- 2021-06-29 Update Added other NSAID pathways as related pathways